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Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 468-475, Oct.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350824


ABSTRACT Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18-69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5-2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5-2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Hydroxyurea , Anemia, Sickle Cell , Tumor Necrosis Factor-alpha , Oxidative Stress , Cytotoxicity, Immunologic , Dosage , Inflammation , Malondialdehyde , Neutrophils
Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 489-493, Oct.-Dec. 2021. tab
Article in English | LILACS | ID: biblio-1350813


ABSTRACT Objective: Low levels of neutrophils can be an intrinsic condition, with no clinical consequences or immunity impairment. This condition is the benign constitutional neutropenia (BCN), defined as an absolute neutrophils count (ANC) ≤2000 cells/mm. Diagnosis of BCN is of exclusion where patients are submitted to blood tests and possibly to invasive diagnostic search until secondary causes of neutropenia are ruled out. The natural history of the disease suggests benign evolution and Brazilian study showed an overall frequency of 2.59%. The main mechanisms include reduced neutrophil production, increased marginalization, extravasation to the tissues and immune destruction. Genetic studies showed strong association between the single nucleotide variant rs2814778 located on chromosome 1q23.2 in the promoter region of the atypical chemokine receptor 1 (Duffy blood group system) gene (ACKR1, also termed DARC) and BCN. The aim of this study is to evaluate FY phenotypes and genotypes including the analysis of the rs2814778 SNP in Brazilian patients with BCN in order to determine an effective diagnostic tool, allowing reassurance of the patient and cost reduction in their care. Methods: Case control study, with 94 individuals (18 patients and 76 controls). Phenotyping was performed by gel test and genotyping was performed by PCR-RFLP. Results: White blood cell (WBC) and absolute neutrophils (AN) counts showed lower levels in patients compared to controls. In the patient group 83.3% were genotyped as FY*B/FY*B. The SNP rs2814778 (-67T > C) was identified in 77.8% of the patients genotyped as FY*B-67C/FY*B-67C. In the control group, 72.7% were homozygous for the wild type and 23.3% were heterozygous. Conclusion: This study reinforces that FY phenotyping and genotyping can be used to detect most people with BCN, avoiding excessive diagnostic investigation. Besides, this procedure may reduce health costs and be reproductible in clinical practice.

Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Duffy Blood-Group System , Genotyping Techniques , Neutropenia , Immunophenotyping , Diagnostic Tests, Routine , Neutrophils
Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 424-429, Oct.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350803


ABSTRACT Introduction: Smoking is associated with the occurrence and progression of cardiovascular diseases, inflammatory disorders and malignancies. Objective: To study the platelet indices, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in smokers and their correlation with smoking pack-years. Method: A total of 110 smokers and 110 non-smokers were included. The smokers were grouped into three groups: mild (<5 pack-years), moderate (5-10 pack-years) and heavy (>10 pack-years). The platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were noted. The NLR and PLR were calculated and the statistical analysis was made using the Student's T-test, Analysis of Variance (ANOVA) and Spearman's correlation coefficient. Results: The platelet count, PCT and PDW were significantly higher with mean values: 218.56 ± 121.31 vs 203.23 ± 80.35 (p-value = 0.038), 0.27 ± 0.10 vs 0.26 ± 0.10 (p-value = 0.041) and 12.54 ± 1.45 vs 11.99 ± 1.70 (p-value = 0.001) in smokers and non-smokers, respectively. The PLR differed significantly with mean values: 119.40 ± 84.81 in smokers and 181.99 ± 313.09 in non-smokers, with a p-value of 0.045. A significant positive correlation was found between pack-years of smoking and platelet count and PLR with the Pearson correlation coefficient of 0.250 and 0.198 and p-values, 0.008 and 0.037, respectively. The Platelet Count, PCT, MPV and PDW varied significantly between mild, moderate and heavy smoker groups, with p-values of 0.045, 0.010, 0.015 and 0.017, respectively. Conclusion: The platelet indices and inflammatory markers NLR and PLR are derived from routine blood investigations, which are easily available and inexpensive. The monitoring of platelet indices, along with the PLR, can be used as early predictors of morbidity in smokers.

Humans , Male , Female , Tobacco Use Disorder , Mean Platelet Volume , Thromboembolism , Lymphocytes , NLR Proteins , Heart Disease Risk Factors , Neutrophils
Arq. bras. med. vet. zootec. (Online) ; 73(6): 1323-1333, Nov.-Dec. 2021. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1355677


Morphological and cytochemical studies of peripheral blood cells of fish have improved the understanding of their functions and cell types. The present study performed the Morphological and cytochemical analysis of the peripheral blood of Prochilodus lineatus, Characiform native to South America, which has been gaining space in local aquaculture and as a species introduced in Asia. Our analysis provided information on the morphological and cytochemical characteristics of the leukocytes, for the formulation of hypothesis about their role in the immune system of the species. It was found that Prochilodus lineatus has morphological and cytochemical features in common with other fish species, mainly of the Characiformes order. However, we detected the presence of heterophils and PAS positive granulocytes simultaneously with neutrophils. We also found that heterophils and PAS positive granulocytes are very similar, both morphologically and cytochemically.(AU)

O estudo da morfologia e da citoquímica das células do sangue periférico dos peixes tem sido eficaz para o entendimento de suas funções e dos tipos celulares. Este estudo realizou a análise morfológica e citoquímica do sangue periférico de Prochilodus lineatus, caracídeo nativo da América do Sul que vem ganhando espaço na aquicultura local e como espécie introduzida na Ásia. Essa análise forneceu informações sobre a morfologia e as características citoquímicas dos leucócitos, visando a hipóteses sobre suas funções. Verificou-se que estas são semelhantes em vários aspectos a outras espécies, principalmente da ordem Characiformes. No entanto, neste estudo detectou-se a presença dos heterofilos e da célula granulocítica especial, simultaneamente à presença dos neutrófilos. Ainda, foi verificado que os heterofilos e a célula granulocítica especial são muito semelhantes morfológica e citoquimicamente.(AU)

Animals , Characiformes/blood , Neutrophils/cytology , Blood Chemical Analysis/veterinary , Histocytochemistry/veterinary
An. bras. dermatol ; 96(5): 574-577, Sept.-Oct. 2021. graf
Article in English | LILACS | ID: biblio-1345148


Abstract Neutrophilic dermatoses encompass a wide spectrum of diseases characterized by a dense infiltration mainly composed of neutrophils. Neutrophilic dermatosis of the dorsal hands is currently considered a localized variant of Sweet syndrome. Cocaine abuse has been related to a wide range of mucocutaneous manifestations, including neutrophilic dermatoses such as pyoderma gangrenosum. The authors of this study present a patient with neutrophilic dermatosis of the dorsal hands, in which cocaine abuse was identified as a probable trigger.

Humans , Sweet Syndrome/diagnosis , Sweet Syndrome/chemically induced , Pyoderma Gangrenosum , Cocaine-Related Disorders/complications , Dermatitis , Neutrophils
Arq. bras. med. vet. zootec. (Online) ; 73(5): 1039-1046, Sept.-Oct. 2021. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1345264


The nasal strip is widely used in horses during exercise, but effects of using a nasal strip are controversial and little is known about its effect on horses undergoing endurance events. The aim of this study was to determine whether the use of nasal strips influences alveolar cell population assessed by bronchoalveolar lavage (BAL), tidal volume, and nasal airflow rate. Six Arabian horses were subjected to two low intensity tests on a treadmill, with and without application of a commercial external nasal strip. Tidal volumes and airflow rates were measured during the test; two hours after the test, BAL was performed to assess cytology of pulmonary secretions. The lavage fluid showed increased neutrophil count after exercise in animals with the nasal strip (P<0.05). This suggests that turbulence of airflow through the nasal cavity may have diminished with nasal strip use, thus allowing larger particles to be deposited more distally in the respiratory system, inducing a more intense neutrophilic response. No differences in tidal volumes or airflow rates were observed between groups (with or without nasal strips) during the test (P>0.05). The use of nasal strips seems to influence alveolar cell population during and after exercise in horses after low intensity exercise tests. Further studies are needed to verify whether alveolar cell population is related to poor exercise performance in horses.(AU)

A fita nasal é amplamente utilizada em equinos durante o exercício, porém seus resultados são controversos e pouco conhecidos em animais que disputam provas de resistência. O objetivo deste trabalho foi verificar se o uso da fita nasal influencia a população de células alveolares por meio de lavado broncoalveolar, volume corrente e fluxo de ar nasal. Foram utilizados seis equinos da raça Árabe, que realizaram dois testes de longa duração em esteira, sendo um teste com a fita e outro sem a fita nasal. Fluxo e volume respiratório foram mensurados durante o teste; duas horas após o término do exercício, foi realizado lavado broncoalveolar para realização de citologia da secreção pulmonar. Foi verificada maior porcentagem de neutrófilos após o exercício nos animais que se exercitaram com a fita nasal (P<0,05), indicando que o turbilhonamento na passagem do ar através da cavidade nasal pode ter diminuído, permitindo que partículas maiores se depositassem em porções mais distais do sistema respiratório, induzindo uma resposta neutrofílica mais intensa. Não houve diferenças entre os parâmetros ventilatórios analisados entre os animais quando correram com ou sem a fita nasal (P>0,05). O uso da fita nasal parece influenciar alguns parâmetros, durante e após o exercício, em animais que realizam provas de longa duração. Outros estudos devem ser realizados para verificar se essa influência pode melhorar o desempenho desses animais em exercícios predominantemente aeróbicos.(AU)

Animals , Bronchoalveolar Lavage Fluid/cytology , Physical Functional Performance , Horses/physiology , Neutrophils , Respiration , Endurance Training/veterinary
Arq. gastroenterol ; 58(2): 131-138, Apr.-June 2021. tab, graf
Article in English | LILACS | ID: biblio-1285331


ABSTRACT BACKGROUND: Individuals with cirrhosis have a chronic systemic inflammation associated with an immune dysfunction, affecting the progression of the liver disease. The neutrophil-lymphocyte ratio (NLR) was proposed as a marker of systemic inflammatory response and survival in patients with cirrhosis. OBJECTIVE: Evaluate the prognostic role of NLR in cirrhotic patients and its relation with inflammatory cytokines(IL-6, IL-10 and IL-17). METHODS: In this prospective study two groups were evaluated: 1) Stable cirrhotic in outpatient follow-up (n=193); 2) Hospitalized cirrhotic for acute decompensation for at least 48 hours (n=334) with admission and 48 hours tests evaluation. Circulating inflammatory cytokines were available for 130 hospitalized patients. RESULTS: In outpatients with stable cirrhosis, NLR correlated with MELD score and other variables associated with severity of disease. However, after a median of 32 months of follow up NLR was not associated with mortality (HR 1.058, 95%CI 0.900-1.243; P=0.495). In hospitalized patients, NLR at 48-hour after admission was independently associated with 90-day survival (HR 1.061, 95%CI 1.020-1.103; P=0.003) in multivariate Cox-regression analysis. The 90-day Kaplan-Meier survival probability was 87% for patients with a 48-hour NLR <3.6 and 62% for NLR ≥3.6 (P<0.001). Elevation of NLR in the first 48 hours was also independently associated with mortality (HR 2.038, 95%CI 1295-3207; P=0.002). The 90-day Kaplan-Meier survival probability was 83% when NLR did not increase and 62% when NLR increased (P<0.001). IL-6, IL-10 and IL-17 at admission were positively correlated with both admission and 48-hour NLR. Lower levels of baseline IL-10 were associated with NLR increase during first 48-hour. CONCLUSION: NLR evaluated at 48 hours of hospitalization and its early increase after admission were independently associated with short-term mortality in patients hospitalized for acute decompensation of cirrhosis.

RESUMO CONTEXTO: Na cirrose há um quadro crônico de inflamação sistêmica associada a disfunção imune, que impactam na progressão da doença hepática. A razão neutrófilo-linfócito (RNL) foi proposta como um marcador de resposta inflamatória sistêmica e sobrevida em pacientes com cirrose hepática. OBJETIVO: Avaliar o papel de RNL como marcador prognóstico em portadores de cirrose hepática e sua relação com citocinas inflamatórias (IL-6, IL-10 e IL-17). MÉTODOS: É um estudo prospectivo com duas coortes: 1) pacientes cirróticos estáveis em acompanhamento ambulatorial (n=193); 2) pacientes cirróticos hospitalizados por descompensação aguda por no mínimo 48 horas (n=334) com avaliação de exames de admissão de 48 horas. Citocinas inflamatórias séricas estavam disponíveis em 130 pacientes hospitalizados. RESULTADOS: Nos pacientes ambulatoriais com cirrose estável, RNL se correlacionou com MELD e outras variáveis associadas com gravidade da doença. Entretanto, após uma mediana de 32 meses de seguimento, RNL não apresentou associação com mortalidade (HR 1.058, 95%CI 0.900-1.243; P=0.495). Nos pacientes hospitalizados, RNL de 48 horas após a admissão apresentou associação independente com sobrevida em 90 dias (HR 1.061, 95%CI 1.020-1.103; P=0.003) na regressão multivariada de Cox. A probabilidade de sobrevivência pela curva de Kaplan-Meier em 90 dias foi de 87% em pacientes com RNL de 48 horas <3.6 e 62% nos pacientes com RNL ≥3.6 (P<0.001). A elevação de RNL nas primeiras 48 horas também foi um fator independente associado a mortalidade (HR 2.038, 95%CI 1295-3207; P=0.002). A avaliação de sobrevida em 90 dias pela curva de Kaplan-Meier foi de 83% nos pacientes em que RNL não apresentou elevação e 62% nos que apresentaram elevação de RNL (P<0.001). IL-6, IL-10 e IL-17 na admissão se correlacionaram positivamente com RNL de admissão e de 48 horas. Níveis mais baixos de IL-10 basal foram associados com elevação de RNL nas primeiras 48 horas. CONCLUSÃO: RNL avaliada em 48 horas de hospitalização e sua elevação precoce após a admissão foram fatores independentemente associados a mortalidade em curto prazo nos pacientes hospitalizados com descompensação aguda da cirrose.

Humans , Lymphocytes , Neutrophils/pathology , Prognosis , Prospective Studies , Retrospective Studies , Liver Cirrhosis/complications , Liver Cirrhosis/pathology
Rev. epidemiol. controle infecç ; 11(1): 46-53, jan.-mar. 2021. ilus
Article in English, Portuguese | LILACS | ID: biblio-1362317


Background and Objectives: cancer cases are gradually increasing, and most treatments still cause several adverse reactions, such as myelosuppression. When neutrophils decline, febrile neutropenia (FN) can be triggered, considered an oncological emergency, leaving patients susceptible to infections. Therefore, it is necessary to determine the best treatment, seeking to reduce the risk of complications. The purpose of this review is to identify, in literature, randomized clinical studies that compare different treatments for FN in pediatric onco-hematological patients. Content: a systematic search was carried out on the PubMed database, for randomized clinical studies, from 2009 to 2019, in English, using "Febrile Neutropenia", "Pediatric", and "Therapeutics" as descriptors. A total of 233 articles were found, seven of which were selected for review. The most described antimicrobial for FN treatment was Piperacillin/Tazobactam (PIP/TAZ) and its use is justified by its spectrum of action to cover the most frequent microorganisms in patients with FN. The possibility of using oral antimicrobials may be an alternative and should be analyzed. The description of the risk classification criteria is essential to guide the therapy, and new tools, such as the stewardship, add safety to patient care. Conclusion: the most used antimicrobial to treat FN was PIP/TAZ, and the establishment of standardized risk classification scores in pediatric onco-hematological patients is essential to guide clinical management in FN treatment.(AU)

Justificativa e objetivos: os casos de câncer estão aumentando gradativamente, e a maioria dos tratamentos ainda causa várias reações adversas, como a mielossupressão. Com o declínio dos neutrófilos, pode-se desencadear a neutropenia febril (NF), considerada uma emergência oncológica, deixando o paciente suscetível a infecções. Portanto, é necessário determinar o melhor tratamento, visando reduzir o risco de complicações. O objetivo desta revisão é identificar, na literatura, estudos clínicos randomizados que comparem diferentes tratamentos para NF em pacientes onco-hematológicos pediátricos. Conteúdo: foi realizada busca sistemática na base de dados PubMed, de estudos clínicos randomizados, no período de 2009 a 2019, na língua inglesa, utilizando como descritores "Febrile Neutropenia", "Pediatric" e "Therapeutics". Foram encontrados 233 artigos, dos quais sete foram selecionados para revisão. O antimicrobiano mais descrito para o tratamento com FN foi Piperacilina / Tazobactam (PIP / TAZ) e seu uso justifica-se por seu espectro de ação para cobrir os microrganismos mais frequentes em pacientes com FN. A possibilidade de uso de antimicrobianos orais pode ser uma alternativa e deve ser analisada. A descrição dos critérios de classificação de risco é essencial para orientar a terapia, e novas ferramentas, como o stewardship, agregam segurança ao atendimento ao paciente. Conclusão: o antimicrobiano mais utilizado para tratar FN foi o PIP / TAZ, e o estabelecimento de escores de classificação de risco padronizados em pacientes onco-hematológicos pediátricos é essencial para orientar o manejo clínico no tratamento de FN.(AU)

Antecedentes y objetivos: los casos de cáncer están aumentando gradualmente y la mayoría de los tratamientos aún causan varias reacciones adversas, como la mielosupresión. Cuando los neutrófilos disminuyen, se puede desencadenar la neutropenia febril (FN), considerada una emergencia oncológica, dejando a los pacientes susceptibles a infecciones. Por tanto, es necesario determinar el mejor tratamiento, buscando reducir el riesgo de complicaciones. El propósito de esta revisión es identificar, en la literatura, estudios clínicos aleatorizados que comparen diferentes tratamientos para la FN en pacientes pediátricos oncohematológicos. Contenido: se realizó una búsqueda sistemática en la base de datos PubMed, de estudios clínicos aleatorizados, de 2009 a 2019, en inglés, utilizando como descriptores "Febrile Neutropenia", "Pediatric" y "Therapeutics". Se encontraron un total de 233 artículos, siete de los cuales fueron seleccionados para revisión. El antimicrobiano más descrito para el tratamiento de FN fue Piperacilina / Tazobactam (PIP / TAZ) y su uso se justifica por su espectro de acción para cubrir los microorganismos más frecuentes en pacientes con FN. La posibilidad de utilizar antimicrobianos orales puede ser una alternativa y debe analizarse. La descripción de los criterios de clasificación de riesgo es fundamental para orientar la terapia, y nuevas herramientas, como la rectoría, añaden seguridad a la atención al paciente. Conclusión: el antimicrobiano más utilizado para tratar la FN fue la PIP / TAZ, y el establecimiento de puntuaciones estandarizadas de clasificación de riesgo en pacientes pediátricos oncohematológicos es fundamental para orientar el manejo clínico en el tratamiento de la FN.(AU)

Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Pediatrics , Febrile Neutropenia , Chemotherapy-Induced Febrile Neutropenia , Medical Oncology , Neutrophils/drug effects , Anti-Infective Agents
Braz. j. med. biol. res ; 54(10): e11409, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285656


Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.

Humans , Female , Breast Neoplasms , Neutrophils , Prognosis , Lymphocytes , Retrospective Studies , Neoplasm Recurrence, Local , Obesity/complications
Braz. J. Pharm. Sci. (Online) ; 57: e19139, 2021. graf
Article in English | LILACS | ID: biblio-1350244


Dehydroepiandrosterone (DHEA) is a steroid hormone secreted by the adrenal glands, gonads and brain. It is a precursor to sex hormones and also is known to have immune modulatory activity. However, little is known about the relationship between DHEA and neutrophils and thus our study evaluates the influence of DHEA in the effector functions of neutrophils. Human neutrophils were treated in vitro with DHEA and further infected with Salmonella enterica serovar Typhimurium. The treatment of neutrophils with 0.01 µM of DHEA increased the phagocytosis of Salmonella independent of TLR4 as the treatment did not modulate the TLR4 expression. Additionally, DHEA caused a decrease in ROS (reactive oxygen species) production and did not influence the formation of the neutrophil extracellular trap (NET). Steroid treated neutrophils, infected or stimulated with LPS (lipopolysaccharide), showed reduced production of IL-8, compared to untreated cells. Also, the protein levels of p-NFκB were decreased in neutrophils treated with DHEA, and this reduction could explain the reduced levels of IL-8. These results led us to conclude that the steroid hormone DHEA has important modulatory functions in neutrophils

Humans , Male , Adult , In Vitro Techniques , Dehydroepiandrosterone/analysis , Neutrophils/metabolism , Phagocytosis/genetics , Gonadal Steroid Hormones/pharmacology , Adrenal Glands/metabolism , Salmonella enterica/classification
J. appl. oral sci ; 29: e20200770, 2021. graf
Article in English | LILACS | ID: biblio-1180798


Abstract Objective Neutrophils are key effector cells of the innate immune system. They recognize antigens through membrane receptors, which are expressed during their maturation and activation. Neutrophils express FcγRII (CD32), FcγRIII (CD16), and FcγRI (CD64) after being activated by different factors such as cytokines and bacterial products. These receptors are involved with phagocytosis of IgG-opsonized microbes and enhance defense mechanisms. Based on that, our study seeks to compare the expression of FcγRII, FcγRIII, FcγRI, and CD11b on neutrophils from elderly and young subjects and their expression after in vitro activation with cytokines and LPS. Methodology Neutrophils were isolated from human peripheral blood and from mice bone marrow by density gradient. After isolation, FCγRs expression was immediately analyzed by flow cytometry or after in vitro stimulation. Results In freshly isolated cells, the percentage of FcγRIIIb+ and CD11b+ neutrophils were higher in samples from young individuals; FcγRIIIa expression was more prominent on aged neutrophils; FcγRIA expression was similar in all samples analyzed. Exposure to CXCL8 and LPS resulted in a higher percentage of FcγRIa+ neutrophils on elderly individuals' samples but lower when compared with neutrophils from young donors. We observed that LPS caused an increase in FcγRIIa expression on aging human neutrophils. In contrast, FcγRIIIb expression in response to CXCL8 and LPS stimulation was not altered in the four groups. CD11b expression was lower in neutrophils from elderly individuals even in response to LPS and CXCL8. In mice, we observed differences only regarding CD11b expression, which was increased on aged neutrophils. LPS exposure caused an increase in all FcγRs. Conclusions Our results suggest that, in humans, the overall pattern of FcγR expression and integrin CD11b are altered during aging and immunosenescence might contribute to age-related infection.

Animals , Mice , Receptors, IgG , Neutrophils , Phagocytosis , Cell Count , Flow Cytometry
Article in Chinese | WPRIM | ID: wpr-888184


Indolealkylamines(IAAs) are the main hydrophilic substances in toad skin, mainly including free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine. In this study, the LPS-activated neutrophils were used to investigate the structure-activity relationship and anti-inflammatory mechanism of the above-mentioned five monomers from the toad skin in vitro. The neutrophils were divided into the control group, model group(1 μg·mL~(-1) LPS), positive drug group(100 μg·mL~(-1) indometacin), as well as the low-(50 μg·mL~(-1)), medium-(100 μg·mL~(-1)) and high-dose(200 μg·mL~(-1)) free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine groups. The levels of IL-6, TNF-α and IL-1β in the neutrophil supernatant of each group was measured by enzyme-linked immunosorbent assay(ELISA) after LPS stimulation, followed by the detection of apoptosis in each group after Annexin V/PI staining. The protein expression levels of caspase-3, Bax, Bcl-2, beclin1, LC3-I, and LC3-Ⅱ were assayed by Western blot. The results showed that IAAs reduced the excessive secretion of inflammatory cytokines caused by LPS compared with the model group. Besides, the activity of each free IAAs(N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine and dehydrobufotenine), especially bufotenine, was stronger than that of the binding bufothionine. As revealed by Annexin V/PI staining, LPS delayed the early apoptosis of neutrophils compared with the control group, while bufotenine promoted the apoptosis of neutrophils in a dose-dependent manner, which might be related to the elevated expression of apoptosis-related protein Bax/Bcl-2. In addition, LPS activated the autophagy pathways in neutrophils. This study confirmed the efficacy of IAAs in reducing the secretion of inflammatory cytokines in neutrophils induced by LPS for the first time. For instance, bufotenine exerts the anti-inflammatory effect possibly by inducing the apoptosis of neutrophils.

Animals , Anti-Inflammatory Agents/pharmacology , Apoptosis , Bufonidae , Lipopolysaccharides/toxicity , Neutrophils , Skin
Article in Chinese | WPRIM | ID: wpr-888081


The present study aims to investigate the effects of the main components(aesculin, berberine hydrochloride, and anemoside B4) in the butyl alcohol extract of Baitouweng Decoction(BAEB) on the chemotaxis of neutrophils induced by dimethyl sulfoxide(DMSO). HL60 cells were cultivated in RPMI-1640 complete medium, and transferred into a 6-well plate(2 × 10~5 per mL) with 4 mL in each well, followed by incubation with DMSO at 1.3% for five days. The morphologic changes of cells were observed under an inverted microscope. The CD11 b expression after DMSO induction was analyzed by flow cytometry. The effects of aesculin, berberine hydrochloride, and anemoside B4 on the cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The effects of the main components on the production and polarization of F-actin protein were also examined by flow cytometry and laser confocal microscopy. PI3 K/Akt signaling pathway was checked by Western blot. As revealed by the results, neutrophil-like HL60 cells were observed after DMSO induction. The CD11 b expression in these cells increased significantly as indicated by the flow cytometry. Additionally, 100 μg·mL~(-1) aesculin, 8 μg·mL~(-1) berberine hydrochloride, and 80 μg·mL~(-1) anemoside B4 were potent in inhibiting the migration of neutrophils and reducing F-actin expression. Berberine hydrochloride was verified to be capable of diminishing phosphorylated PI3 K/Akt protein expression. The findings indicate that aesculin, anemoside B4, and especially berberine hydrochloride in the BAEB can inhibit the chemotaxis of neutrophils, which is possibly achieved by the inhibition of F-actin and PI3 K/Akt signaling pathway.

1-Butanol , Berberine/pharmacology , Chemotaxis , Drugs, Chinese Herbal/pharmacology , Neutrophils
J. venom. anim. toxins incl. trop. dis ; 27: e20200179, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1279402


Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)

Animals , Poisons/administration & dosage , Reactive Oxygen Species , NADPH Oxidases , L-Amino Acid Oxidase , Neutrophils , Anti-Inflammatory Agents
Pesqui. vet. bras ; 41: e06652, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1180875


Painful procedures can affect the function of innate immune cells, such as neutrophils and macrophages, increasing the risk of infectious diseases. The present work aimed to verify if the analgesics flunixin meglumine or ketoprofen can attenuate the pain/discomfort of newborn lambs submitted by elastration tail docking and thereby avoid the impairment of blood granulocytes function. Twenty-one neonate lambs were divided into three treatments: the control group (n=7), not subjected to caudectomy; the flunixin group (n=7), subjected to caudectomy under local anesthesia and analgesia with two doses of flunixin meglumine; and the ketoprofen group (n=7), subjected to caudectomy under local anesthesia and two doses of ketoprofen. Pain indicators were observed by pain posture score (PS), the number of vocalizations (V), frequency of the movement of the ears (EF), and respiratory rates (RR), observed by a 10 minutes videos for each time points: -15min, 6h, 48h, and 144h. At the same time points, the reactive oxygen species (ROS) production and phagocytosis of blood granulocytes were measured by flow cytometry. At 6h after caudectomy, there was a pain indicator increase (RR, V, and PS), a blood granulocyte percentage increase, and a granulocytes phagocytosis reduction for both groups. At 48h, the ketoprofen group spend more time in pain posture and, at 144h, they exhibited a ROS production granulocyte reduction without signs of pain. We conclude the flunixin meglumine and ketoprofen did not prevent the acute pain/discomfort caused by caudectomy, because the groups showed a pain behavior and impaired of the innate immune response however, the flunixin meglumine was effective in controlling the chronic pain and their effects on blood granulocytes function in compare ketoprofen.(AU)

Procedimentos dolorosos podem afetar a função das células imunes inatas como neutrófilos e macrófagos, aumentando o risco de ocorrer doenças infeciosas. Desta maneira, o presente trabalho pretendeu verificar se os analgésicos flunixin meglumine ou cetoprofeno conseguem atenuar a dor/desconforto de cordeiros neonatos submetidos a caudectomia por elastração, evitando assim o comprometimento da função dos granulócitos sanguíneos. Para tanto 21 cordeiras foram aleatoriamente divididas em três tratamentos: grupo controle (n=7) não submetido a caudectomia, grupo flunixin (n=7) submetido a caudectomia precedida por anestesia local e duas doses de flunixin meglumine, e cetoprofeno (n=7) submetido a caudectomia precedida por anestesia local e duas doses de cetoprofeno. Mensurou-se os indicadores de dor/desconforto após caudectomia por observações de escore de postura de dor (EP), número de vocalizações (V), frequência de movimentar as orelhas (FO) e frequência respiratória (FR), observados em vídeos de 10 minutos nos momentos -15 min e 6, 48 e 144h. Nos mesmos momentos, avaliou-se a as funções de produção de espécies reativas de oxigênio (ERO) e de fagocitose por granulócitos sanguineos em citometria de fluxo. Notou-se aumento dos indicadores de dor (FR, de V e de EP), da porcentagem dos granulócitos sanguíneos e redução da eficiência de fagocitose em ambos os grupos as 6h. As 48h, os animais do grupo cetoprofeno ainda apresentava mais tempo em postura de dor que os demais grupos e as 144h, apresentou redução da produção ERO por granulócitos. Tais achados permitem concluir que tanto o flunexin meglumine como o cetoprofeno não preveniram dor/desconforto agudo promovido pela elastração, pois os dois grupos manifestaram comportamento de dor e redução da resposta imune inata. Ainda, o analgésico flunixin meglumine foi efetivo em controlar a dor mais tardia e seus efeitos na função de granulócitos sanguíneos em comparação ao cetoprofeno.(AU)

Animals , Female , Phagocytosis , Sheep , Ketoprofen , Analgesia , Neutrophils , Reactive Oxygen Species
Pesqui. vet. bras ; 41: e06880, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1287517


This study aimed to assess liver damage and interferon-stimulated gene 15 (ISG15) blood expression as a consequence of embryonic signaling on maternal recognition of pregnancy in beef cattle presenting natural ingestion of Senecio spp. Epidemiological aspects, as the presence of the plant, associated to gamma glutamyl transferase (GGT) activity can be used as Senecio spp. poisoning diagnosis. Maternal recognition of pregnancy period occurs when the embryo secretes interferon tau (IFNT) to signal its presence to the mother and eventually extend corpus luteum (CL) lifespan. In our study, liver damage was determined by concentration serum GGT, cytological and histopathological examinations. Reproductive status was evaluated by concentration of progesterone, CL diameter and ISG15 mRNA expression on Day 19 following fixed-time artificial insemination (FTAI). Cows were categorized into two groups based on concentration of GGT: Group 1 (GGT<30U/L) and 2 (GGT>31U/L). No difference on body condition scores was observed. All the cows presented liver damage based on cytology and histopathological exams. Cows from the Group 1 had higher pregnancy rate, presenting larger CL diameter and greater concentration of progesterone. Interestingly, ISG15 mRNA expression had no difference between Groups 1 and 2, even presenting difference in pregnancy status. These findings suggest embryonic loss beyond Day 19. It suggests late embryonic mortality may be associated to liver insufficiency. In conclusion, liver injury and/or concentration of GGT does not alter ISG15 expression on blood neutrophils, however cows presenting lower concentration of GGT (<30U/L) had increased pregnancy status. Therefore, the concentration of GGT allow us to screen liver status and foresee a successful pregnancy in beef cattle.(AU)

O objetivo deste estudo foi avaliar a lesão hepática e a expressão sanguínea do gene estimulado por interferon 15 (ISG15) durante a sinalização embrionária, no reconhecimento materno da gestação, em bovinos de corte apresentando ingestão natural de Senecio spp. Fatores epidemiológicos, como a presença da planta, associados à atividade da gama glutamil transferase (GGT) podem ser utilizados como diagnóstico da intoxicação por Senecio spp. O reconhecimento materno da gestação ocorre quando o embrião secreta interferon tau (IFNT) para sinalizar sua presença à mãe. Em nosso estudo, a lesão hepática foi determinada pela concentração sérica de GGT, pelos exames citológicos e histopatológicos. O estado reprodutivo foi avaliado pela concentração de progesterona, diâmetro de corpo lúteo (CL) e expressão de mRNA ISG15 no Dia 19 após a inseminação artificial em tempo fixo (IATF). As vacas foram separadas em dois grupos com base na concentração de GGT sanguíneo: Grupo 1 (GGT<30U/L) e Grupo 2 (GGT>31U/L). Não foi observada nenhuma diferença no escore de condição corporal entre os grupos. Na citologia e nos exames histopatológicos todas as vacas apresentaram lesão hepática. As vacas do Grupo 1 apresentaram maior taxa de prenhez, maior diâmetro do CL e maior concentração de progesterona. Diferente do esperado, a expressão do mRNA ISG15 não foi diferente entre os Grupos 1 e 2, mesmo apresentando diferença na taxa de prenhez. Esses achados sugerem perda embrionária após o Ddia 19. Isso demonstra que a mortalidade embrionária tardia pode estar associada à insuficiência hepática. Dessa forma, conclui-se que a lesão hepática e/ou concentração de GGT não altera a expressão de ISG15 nos neutrófilos sanguíneos, porém vacas com menor concentração de GGT (<30U/L) apresentaram maiores taxas de prenhez. Assim, a concentração de GGT nos permite avaliar a saúde hepática e prever uma gestação bem-sucedida em bovinos de corte.(AU)

Animals , Cattle , Plants , Poisoning , Progesterone , Senecio , Cattle/blood , Insemination, Artificial , Gene Expression , Interferons , Neutrophils , Mortality , Corpus Luteum
Article in Chinese | WPRIM | ID: wpr-880042


OBJECTIVE@#To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM).@*METHODS@#The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared.@*RESULTS@#ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P<0.05). There were no significant difference in age, sex, serum calcium (Ca), β @*CONCLUSION@#Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.

Blood Platelets , Humans , Lymphocytes , Monocytes , Multiple Myeloma , Neutrophils , Prognosis , Retrospective Studies
Article in English | WPRIM | ID: wpr-879941


Bronchial asthma is a chronic respiratory disease,characterized by airway inflammation,airway hyperresponsiveness,reversible airway obstruction and airway remodeling,in which a variety of cells including airway inflammatory cells and structural cells are involved. Previous studies have shown that asthma is mainly driven by Th2 cytokines IL-4,IL-5,and IL-13,leading to airway eosinophil inflammation. With further research,however,it has been found that neutrophils are also closely related to asthma. Numbers of neutrophils are elevated in airway through increased chemotaxis and decreased apoptosis,which is earlier than eosinophils,leading to airway neutrophilic inflammation. Neutrophils can produce elastase,myeloperoxidase,neutrophil extra- cellular traps,chemokines and cytokines,participating in the occurrence and development of asthma. The antagonists against these molecules,such as anti-IL-8 receptor antibody,anti-IL-17 antibody,and DNase,have shown positive effects on neutrophilic asthma,but further studies are needed to support their clinical application. This article mainly reviews the role of neutrophils in asthma and related mechanisms.

Asthma/immunology , Cytokines , Eosinophils , Humans , Inflammation , Neutrophils/immunology