Emerging Role of Mast Cells as Biological Markers in the Pathogenesis of Infectious Diseases and their Projection in Health Emergencies

SUMMARY: Mast cells (MC) are cells of the immune system that regulate cell and tissue homeostasis, are found in low numbers, have an intact plasma membrane, and a cytoplasm with a wide variety of inflammatory chemical mediators. The activation or degranulation of mast cells implies the release of these chemical mediators (interleukins, cytokines, and more), causing tissue actions ranging from the activation of metalloproteinases to the development of anaphylactic hypersensitivity of different degrees, alterations in vascular permeability, and loss of cell homeostasis. This behavior would allow them to act as sentinels responding to pathophysiological processes. During the COVID-19 pandemic, in positive human patients, the available literature reports the presence and degranulation of mast cells in a generalized manner, especially in the respiratory tract. This study aimed to analyze the emerging role of MCs in the pathogenesis of diseases and their projection as biological markers in the treatment of diseases or pandemics. The analysis of human biopsies showed that MCs are observed as cells with diameters between 8 to 20 µm, and in inflamed tissues, degranulation of MCs is observed. The action of MCs degranulation was related to different inflammatory processes of autoimmune diseases. It is concluded that the potential of MC as therapeutic targets and biomarkers could raise new pharmacological targets, as supportive therapy, and possibly of great help in the treatment of future emerging pandemics such as the current monkeypox.

Los mastocitos (MC) son células del sistema inmune que regulan la homeostasis celular y tisular, se encuentran en escasas cantidades, presentan una membrana plasmática íntegra, y un citoplasma con una amplia variedad de mediadores químicos. La activación o degranulación de los mastocitos implica la liberación de estos mediadores químicos (interleuquinas, citoquina y más), provocando acciones tisulares que van desde la activación de metaloproteinasas hasta el desarrollo de hipersensibilidad anafiláctica de distinto grado, provocando la pérdida de la homeostasis celular. Durante la pandemia de la COVID-19, en pacientes humanos positivos, se informa recurrentemente la presencia y degranulación de mastocitos de manera generalizada sobre todo en las vías respiratorias. El análisis de la degranulación de los MCs podría proporcionar información que podría utilizarse en el desarrollo de tratamientos preventivos contra infecciones virales, bacterianas u otros patógenos. Este comportamiento les permitiría actuar como centinelas en respuesta a procesos fisiopatológicos. El objetivo de este trabajo fue analizar el rol emergente de los MCs en la patogenia de enfermedades y su proyección como marcadores biológicos en el tratamiento de enfermedades o pandemias. En análisis de biopsias humanas se muestran que MCs se observan como células con diámetros de entre 8 a 20 µm, en tejidos inflamados se observa degranulación de MCs. Se relacionó el accionar de degranulación de los MCs en diferentes procesos inflamatorios de enfermedades autoinmunes. Se concluye que el potencial de MC como dianas terapéuticas y biomarcadores podrían plantear nuevos objetivos farmacológicos, como terapia de apoyo, y posiblemente de gran ayuda en el tratamiento de futuras pandemias emergentes como la actual viruela del mono.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Mastócitos e síndrome de ativação mastocitária: o que há de novo? / Mast cells and mast cell activation syndrome: what's new?

Os mastócitos são as principais células efetoras da resposta alérgica aguda, desempenhando também um papel importante na angiogênese, tolerância imunológica, regulação da fibrinólise, regeneração neuronal e osteoclastogênese. Localizam-se maioritariamente na pele e nas mucosas do intestino e pulmões, onde exercem uma função "sentinela". As síndromes de ativação mastocitária são caracterizadas pela ocorrência de episódios recorrentes de manifestações clínicas resultantes da libertação de mediadores mastocitários. Esta constitui-se como entidade complexa com um espectro de sintomas associados, representando um desafio diagnóstico e terapêutico. Nesta revisão, os autores pretendem apresentar uma visão geral sobre a estrutura e função dos mastócitos e sobre os critérios diagnósticos e abordagem terapêutica da síndrome de ativação mastocitária.

Mast cells are the main effector cells of acute allergic response, also playing an important role in angiogenesis, immune tolerance, regulation of fibrinolysis, neuronal regeneration, and osteoclastogenesis. They are generally located in the skin and mucous membranes of the intestines and lungs, where they perform a "sentinel" function. Mast cell activation syndrome is characterized by recurrent clinical manifestations resulting from the release of mast cell mediators. This complex entity, which involves a spectrum of associated symptoms, is a diagnostic and therapeutic challenge. In this article we overview of the structure and function of mast cells, in addition to the diagnostic criteria and therapeutic approaches to mast cell activation syndrome.

Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Evaluation of peripheral nerve fibers and mast cells in burning mouth syndrome

Abstract Emerging evidence has revealed a cross-talk in the etiopathogenesis of burning mouth syndrome (BMS) related to peripheral nerve fibers (NF) and neuropeptides secreted by mast cells. Here, we investigated the S-100+ density and PGP 9.5+ integrity of peripheral NF and the tryptase+ mast cell density in the oral mucosa of BMS patients and healthy individuals. A total of 23 oral mucosa specimens (12 BMS and 11 controls) were evaluated. The clinical diagnosis of BMS was based on a careful examination, excluding other local and systemic causes. Samples were taken from an incisional biopsy of the tongue mucosa of individuals with symptomatic BMS, while the margins of the non-neoplastic tongue biopsy served as controls of healthy individuals. Immunohistochemistry was performed to determine the density/mm2 of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells. Similar densities of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells were found in cases of BMS, with a median value of 3.70, 0.70, and 29.24/mm2, respectively, and in the control group, with a median value of 2.60, 0.80, and 26.01/mm2, respectively (p > 0.05). Moreover, the relationship between S100+ and PGP 9.5+ peripheral NF was the same in both groups (p = 0.70). This study demonstrated that there were no alterations in the density and integrity of peripheral NF in the tongue of symptomatic BMS patients. However, the sensitization of peripheral NF in this disease may not depend on mast cell density.

Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells / 中国药房

OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject， and substance P as positive control， the activation effects of 25， 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase， histamine release， and the contents of inflammatory factors； using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 （MRGPRX2） high-expression human embryonic kidney cell line HEK293 （MRGPRX2/ HEK293 cells） as subject， the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase， and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25， 50， 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells （P＜0.05）， and promote the release of tumor necrosis factor-α， interleukin-8， macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees （P＜0.05）. After knocking down MrgprX2， the effects of 25， 50， 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly （P＜0.05）， resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.

Effects of catgut embedding and PGLA embedding at "Zusanli" (ST 36) on skin mast cells, substance P and histamine in healthy rats / 中国针灸

OBJECTIVE@#To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding.@*METHODS@#One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells.@*RESULTS@#There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05).@*CONCLUSION@#Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.

Progress in the treatment of chronic spontaneous urticaria: insights from the changes in the understanding of its pathogenesis / 中华皮肤科杂志

Mast cells, autoantibodies, inflammatory cells, coagulation cascade, complement system and nervous system are all involved in the complex pathogenesis of chronic spontaneous urticaria (CSU) , while mast cells play a pivotal role in it. With deeper understanding of the pathogenesis of CSU, cutting-edge therapeutic methods are gradually being used in clinical practice. Nowadays, pharmacotherapyeutic studies are more focused on accurately modulating the pathological state of mast cells. This review summarizes recent advances in the pathogenesis of and medicines for CSU.

Presence of mast cells in the rat pericranium ­ a tissue very sensitive to pain / Presença de mastócitos no pericrânio do rato ­ tecido muito sensível à dor

Objective: To evaluate mast cell presence in the pericranium of Wistar rats. Methods: Five male rats of the Wistar strain were used. The animals were housed under a 12 h light cycle with ad libitum access to food and water and allowed 10 days of acclimatization before tissue sampling. The five rats were anesthetized by intraperitoneal injection of ketamine/xylazine, 10/20 mg/kg. Following aseptic preparation of the head skin, a midline longitudinal incision was made to expose the pericranium. Two samples of the pericranium were taken, one from the right and one from the left. These samples were fixed in 10% buffered formaldehyde for 24 h. After fixation, tissue samples were paraffin-embedded and sectioned at 4 µm. Then, slides were deparaffinized, stained with a concentration of 0.1% toluidine blue for 1 min, and washed with distilled water. Last, slides were photomicrographed under 400x magnification to identify mast cells. Results: Mast cells were identified in the dura mater and the five rats' pericranium. In the dura mater, mast cells were also found in these rats. We found both granulated (intact) and degranulated mast cells. Conclusion: We suggest that future preclinical studies investigating the involvement of dural mast cells and other meningeal cell populations should also include pericranium samples to explore this structure's relevance in migraine pain and other headache disorders.

Objetivo: Avaliar a presença de mastócitos no pericrânio de ratos Wistar. Métodos: Foram utilizados cinco ratos machos da linhagem Wistar. Os animais foram alojados sob um ciclo de luz de 12 horas com acesso ad libitum a comida e água e tiveram 10 dias de aclimatação antes da amostragem de tecido. Os cinco ratos foram anestesiados por injeção intraperitoneal de cetamina/xilazina, 10/20 mg/kg. Após preparação asséptica da pele da cabeça, foi feita uma incisão longitudinal na linha média para expor o pericrânio. Foram retiradas duas amostras do pericrânio, uma da direita e outra da esquerda. Essas amostras foram fixadas em formaldeído tamponado a 10% por 24 horas. Após a fixação, as amostras de tecido foram embebidas em parafina e seccionadas a 4 µm. Em seguida, as lâminas foram desparafinizadas, coradas com concentração de azul de toluidina 0,1% por 1 min e lavadas com água destilada. Por fim, as lâminas foram fotomicrografadas com aumento de 400x para identificação de mastócitos. Resultados: Foram identificados mastócitos na dura-máter e no pericrânio dos cinco ratos. Na dura-máter, mastócitos também foram encontrados nesses ratos. Encontramos mastócitos granulados (intactos) e desgranulados. Conclusão: Sugerimos que futuros estudos pré-clínicos que investiguem o envolvimento de mastócitos durais e outras populações de células meníngeas também incluam amostras de pericrânio para explorar a relevância desta estrutura na dor da enxaqueca e em outros distúrbios de cefaleia.

Prognostic significance of mast cells and vascular density in prostatic adenocarcinoma

Context: Though mast cells infiltrate solid tumors, the exact role of mast cells in tumor biology is controversial. Mast cell density (MCD) may vary depending on its location in the tumor and tumor vascularity. MCD may influence the tumor aggressiveness. Aims: This study evaluates MCD and tumor vascularity in different histopathological grades of adenocarcinoma prostate. Settings and Design: Descriptive study with purposive sampling. Methods and Material: The subjects of study were 42 adenocarcinoma patients. 20 cases were of intermediate grade (Gleason score 2–7) and 22 were of high-grade (Gleason score 8-10). Histological diagnosis was made by examining sections stained with hematoxylin and eosin. Additional sections from the same block were stained for mast cells using Giemsa stains as per standard protocol. Mast cell count was done in minimum six random high-power microscopy fields in four different regions- intratumoral, peritumoral, stromal and perivascular regions. Statistical Analysis Used: SSPS software version 13.0. Descriptive statistics, Student's t test and ANOVA test. Results: In high-grade adenocarcinoma, mast cell counts were higher in perilesional, stromal and perivascular regions, whereas it was lower in intralesional areas as compared to the intermediate grade. However, statistical significance was observed only for the perivascular region. There was significantly higher number of blood vessels in high-grade adenocarcinoma as compared to intermediate grade adenocarcinoma. Conclusions: In this study, perilesional mast cells and vascularity increased with increased severity of adenocarcinoma. These findings suggest a possible influence of mast cells on the tumor microenvironment such as vessel density and aggressiveness of tumor. However, further studies are required to substantiate results of this study.

Mastocitosis del adulto: reporte de un caso / Adult mastocytosis: a case report

RESUMEN La mastocitosis es una enfermedad heterogénea, caracterizada por una acumulación de mastocitos en uno o más órganos, siendo el más afectado la piel. Es más frecuente en niños, pero también se presentan casos en los adultos. Hay diferencias significativas entre las formas de presentación en estos grupos etarios, así como también en su evolución y pronóstico. Presentamos el caso clínico de una paciente con mastocitosis cutánea de inicio en la adultez.

ABSTRACT Mastocytosis is a heterogeneous disease, characterized by an accumulation of mast cells in one or more organs. The skin being is the most frecuently affected organ. It is more common in children, but cases also occur in adults. There are significant differences between the forms of presentation in these age groups, as well as in their evolution and prognosis. We report the case of a patient with adult-onset cutaneous mastocytosis.

Prognostic Significance of Lymphatic Vessel Density by D2-40 Immune Marker and Mast Cell Density in Invasive Breast Cancer: A Cross Sectional Study at Tertiary Care Hospital in South India.

Background: Tumour induced lymphangiogenesis plays a crucial role in metastasis and tumour progression. The intratumoural and peritumoral lymphatics are supposed to have different biological effects. The aim of present study was to investigate the correlation of intratumoral lymphatic vessel density (I LVD), peritumoral lymphatic vessel density (P LVD), intratumoral mast cell density (I MCD) and peritumoral mast cell density (P MCD) with prognostic parameters in primary breast carcinoma. Methods: Lymphangiogenesis was detected using D2-40 monoclonal antibody and mast cell by using toludine blue stain in 50 cases of primary breast carcinoma. Positively stained lymphatic vessels were counted at 40 x in dense lymphatic vascular foci (hot-spot) within the tumour. Chi square, ANOVA test and Pearsons correlation was applied to determine the relationship amongst various variables, with statistical significance set at p <0.05. Results: Mean P LVD was significantly higher than I LVD (6.25±21 vs 2.75±2.27,p <0.005). Significant correlation was noted between I LVD and P LVD and age, tumour laterality, tumour size and overall staging. However, there was no correlation between I LVD and P LVD with other important clinicopathologic prognostic markers like grade, lymphnode status and lymphovascular invasion. MCD was higher in both intratumoral and peritumoral location as compared to normal tissue. There was an association noted between P MCD with pathological staging and perineural invasion. However, there was no significant association of I MCD and P MCD with other prognostic markers like grade and lymphnode status. No significant correlation was noted between I LVD, P LVD, I MCD and P MCD. Conclusion: The evidences from our study support the utility of D2-40 stain in determining the lymphatic density in IBC. The study findings also establish the existence of lymphangiogenesis in both intratumoral and peritumoral location. For now, the data presented herein do not permit us to promote the utility of LVD and MCD as predictors of prognosis in invasive breast carcinoma.

The Role of Mast Cells on Tumor Occurrence and Development / 中国生物化学与分子生物学报

Mast cells are one of the major immune cells in the human body and best known for their role in allergy and anaphylaxis. The main structural characteristic of mast cells is that they contain a large number of basophilic granules, and the basophilic granules are rich in a variety of bioactive substances including histamine, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP), tryptase, chymase and a diverse number of inflammatory mediators. Histamine is involved in the proliferation, migration and invasion of some kinds of cancer cells, and VEGF, FGF, MMP, tryptase and chymotryptase play a significant role in different stages of tumor angiogenesis. The release of various inflammatory mediators from mast cells can lead to inflammatory response at the site of tumor formation, and it is well known that chronic inflammation is a primary risk factor for cancer development and progression. Some studies have shown that a significantly increased number of mast cells can be detected in different tumor tissues. The active substances released by mastcells can stimulate tumor growth, tumor angiogenesis and promote tumor metastasis. Furthermore, the tumor microenvironment also plays an important role in regulating the recruitment of mast cells to tumor tissues and the maturation and activation of mast cells. In this article, we will review the latest progress in the effects of mast cells on tumor growth, tumor angiogenesis, and tumor microenvironment on mast cellactivation.

A comparative study of two methods to construct allergic contact dermatitis in mice / 中国药理学通报

Abstract; Aim To explore the differences of 2,4-dinitrofluoro- benzene ( DNFB) -induced allergic contact demiatitis (ACD) models with different modeling cycles for the study of skin itch¬ing and inflammation, so as to provide reference and basis for the identification and selection of a more suitable animal model.Methods DNFB was used as a sensitizer, 0.5% DNFB was used to build a 2-week ACD model, and after 5-day sensitiza¬tion, the modeling site was administered once every other day and repeated four times.0.15% DNFB was used to build a 5- week ACD model, and after one week of treatment, DNFB was applied to the modeling site twice a week for four weeks.Behav¬ioral videos were recorded for 60 minutes alter each application of DNFB on the back of the neck for 24 hours.After modeling, Ig-K levels in serum were detected by KLISA, and the skin at the modeling site was stained for histopathology and observed.Results The entire modeling process of both modeled ACD mice was accompanied by severe scratching response after re¬peated skin exposure to DNFB, and the number of scratching significantly increased (P <0.01).Histopathological results showed epidermal thickening ( P < 0.01 ) , hyperkeratosis and inflammatory cell infiltration (P <0.01) in both modeling meth¬ods, and senmi Ig-F levels were significantly elevated ( P < 0.01).Conclusions The contact dennatitis model caused by DNFB is very stable, showing typical pruritus symptoms, severe dermatitis injury and inflammatory immune response, but the 5- week model may have more typical symptoms and allow enough time to observe the effect of the drug, which provides further ex¬perimental basis and evidence for pruritus and inflammation re¬lated drug research.

Role of mast cells in the pathogenesis of allergic contact dermatitis / 中华皮肤科杂志

Allergic contact dermatitis (ACD) is a T cell-mediated inflammatory skin disease induced by contact allergens. The role of mast cells in ACD remains controversial. In the sensitization phase, mast cells play a pro-inflammatory role by releasing inflammatory cytokines to promote recruitment of neutrophils, and affect the sensitization process by stimulating or inhibiting the migration of dendritic cells. During the elicitation phase, mast cells promote non-allergen-specific inflammation, and enhance allergen-specific inflammation in moderate ACD, but inhibit allergen-specific inflammation in severe and chronic ACD. In addition to the IgE-Fcε receptor I-histamine pathway, Mas-related G-protein coupled receptor B2/X2 (MrgprB2/X2) can mediate the activation of mast cells, leading to the release of tryptase to drive non-histaminergic itch, and may serve as a new target for the treatment of ACD.

Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD).@*METHODS@#Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA.@*RESULTS@#Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01).@*CONCLUSION@#EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.

Comparison of macrolide resistance, molecular characteristics and MAST types of Bordetella pertussis collected from Xi’an and Shanghai / 西安交通大学学报(医学版)

【Objective】 To compare the macrolide resistance, molecular characteristics and multilocus antigen sequence typing (MAST) of Bordetella pertussis (Bp) collected from Xi’an and Shanghai so as to provide reference for prevention of pertussis and optimize vaccination strategies. 【Methods】 Erythromycin, azithromycin and clarithromycin susceptibility of clinical isolates collected from Xi’an and Shanghai during 2018 and 2019 were determined by E-test. PCR was used to detect the drug-resistant genes and mutation sites. MAST was employed to do molecular typing for the strains. The differences in macrolide resistance and MAST types between Xi’an and Shanghai were compared. 【Results】 Totally 34 strains from Xi’an and 26 strains from Shanghai were isolated. There were differences between Xi’an and Shanghai in the macrolide resistance (χ2=13.650, P<0.001). The composition ratio of MAST types of pertussis strains was also different between Xi’an and Shanghai (χ2=18.642, P<0.001) in that the prn1/ptxP1/ptxA1/fim3-1/fim2-1 strains dominated in Xi’an, while the prn1/ptxP1/ptxA1/fim3-1/fim2-1 and prn2/ptxP3/ptxA1/fim3-1/fim2-1 were almost half and half in Shanghai. A2047G site mutation was detected in all the macrolide-resistant strains, but not in all sensitive strains. Methylase genes ermA and ermB were detected in some macrolide-resistant strains. No other macrolide-resistant genes were found in resistant strains and no mutation or drug resistance gene was found in all the susceptible strains. 【Conclusion】 Differences existed between Xi’an and Shanghai in the macrolide resistance and MAST types of Bordetella pertussis strains. Further monitoring of Bordetella pertussis in China is required to better understand the resistance and evolution of the pathogen.

Lesiones plantares en paciente pediátrico: apropósito de dos casos / Sole of feet lesions in pediatric patients: a purpose of two cases

RESUMEN Las mastocitosis e histiocitosis, son enfermedades que se caracterizan por la proliferación o activación descontrolada y posterior acumulación anormal de mastocitos e histiocitos respectivamente. De incidencia desconocida, talvez porque son subdiagnosticadas. Su patogenia aún es desconocida, si bien está relacionada con mutaciones en la vía del C-KIT para las mastocitosis y de origen viral o neoplásico en el caso de las histiocitosis. Ambas patologías suelen ser frecuentes en la infancia, incluso algunas son congénitas. El mastocitoma cutáneo único sería una forma benigna de mastocitosis y la histiocitosis de células de Langerhans es una forma de histiocitosis que en nuestro caso al afectar un solo órgano (la piel) tendría un buen pronóstico.

SUMMARY Mastocytosis and histiocytosis are diseases that are characterice by uncontrolled proliferation or activation and subsequent abnormal activation of mast cells and histiocytes respectively. Of unknown incidence, perhaps because they are underdiagnosed, their pathogenesis is still unknown although it is related to mutations in the C-KIT pathway for mastocytosis and of viral or neoplastic origin in the case of histiocytosis. Both pathologies are usually frequent in childhood, even some are congenital. The single cutaneous mastocytoma would be a benign form of mastocytosis and the histiocytosis of Langerhans cells is a form of histiocytosis that in our case affecting a single organ (the skin) will have a good prognosis.

Involvement of tryptase-positive mast cells and angiogenesis in the growth of inflammatory odontogenic cysts

Abstract: Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.

Glaucocalyxin A attenuates allergic responses by inhibiting mast cell degranulation through HMGB1/TLR4/NF-κB signaling pathways / 药学学报

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.