Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis

Abstract: Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

Expression of adhesion molecules on CD34+ cells from steady-state bone marrow before and after mobilization and their association with the yield of CD34+ cells

BACKGROUND: Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors. METHODS: Three-color cytofluorometric analysis was used to compare the expressions of CAMs and chemokines in the bone marrow before and after mobilization. RESULTS: For all studied groups, CAM expression among those with good and poor yields of CD34+ cells was significantly correlated with VCAM-1 (P=0.007), CD44 (P=0.027), and VLA-4 (P=0.014) expressions. VCAM-1 (P=0.001), FLT-3 (P=0.001), CD44 (P=0.011), VLA-4 (P=0.001), and LFA-1 (P=0.001) expressions were higher before HPC mobilization than after HPC mobilization. By contrast, the expression of CXCR4 significantly varied before and after mobilization only among those with successful PBSC mobilization (P=0.002). CONCLUSION: We attempted to identify particular aspects of CAMs involved in CD34+ cell mobilization, which is a highly complex mechanism that involves adhesion molecules and matrix metalloproteases. The mechanism by which CD34+ cell mobilization is activated through proteolytic enzymes is not fully understood. We believe that CXCR4, VLA-4, CD44, and VCAM-1 are the most important molecules implicated in HPC mobilization, particularly because they show a correlation with the yield of CD34+ cells collected via large volume leukapheresis.

Monitoreo de anticuerpos anti-HLA en pacientes con insuficiencia renal crónica en lista de espera para trasplante / Anti-hla antibodies monitoring in patients with chronic re- nal failure on waiting list for renal transplant in Paraguay

INTRODUCCIÓN: El estudio de anticuerpos anti-HLA en el suero del paciente en lista de espera para trasplante renal es fundamental para optimizar la elección de un donante así como el esquema de inmunosupresión de inducción y mantenimiento acorde al riesgo inmunológico. Estos anticuerpos pueden Encontrarse de manera preexistente al trasplante como resultado de exposición del individuo a transfusiones sanguíneas, embarazos y trasplantes previos. El objetivo del estudio fue determinar la incidencia de inmunización frente a antígenos de HLA, los factores asociados y su impacto en pacientes en espera de un trasplante renal. MATERIAL Y MÉTODOS: En este estudio, observacional retrospectivo de corte trasversal, fueron incluidos 254 pacientes en lista de espera para trasplante renal que acudieron al Laboratorio Central de Salud Pública en el período comprendido entre julio de 2013 y julio de 2015. RESULTADOS: De los 254 pacientes estudiados, 30% presentaron anticuerpos anti-HLA. El evento sensibilizante más significativo fue la exposición a un trasplante previo, presentando anticuerpos anti-HLA el 84% de los candidatos a retrasplante (p<0,05). En segundo lugar se encontraron las mujeres multíparas, presentando un PRA (Panel Reactivo de Anticuerpos) positivo el 69% de ellas (p<0,05). Por último, el 24% de los pacientes poli-transfundidos presentaron anticuerpos anti HLA (p<0,05). CONCLUSIONES: En el trascurso de los dos años de estudio, 51 pacientes fueron trasplantados, de los cuales un solo paciente presentaba anticuerpos anti-HLA antes del trasplante. Esto indica claramente que la inmunización frente a antígenos de HLA representa una barrera para el acceso al trasplante

INTRODUCTION: Anti-HLA antibodies determination in the serum of patients on a waiting list for renal transplant is essential to optimize donor selection as well as for the induction and maintenance immunosuppression scheme, according to immunological risk. These antibodies could be present before transplantation as a result of being exposed to blood transfusions, pregnancies and previous transplants. The objective of the study was to determine immunization against HLA antigens, associated factors and their impact on the waiting list for a renal transplant. METHODS: In this observational retrospective cross sectional study, 254 patients on the waiting list for renal transplant were included. These patients attended the Public Health central laboratory between July 2013 and July 2015. RESULTS: 30% of the 254 studied patients presented anti-HLA antibodies. The most significant sensitizing event was the exposure to a previous transplant (p=<0.05). Multiparous women were in second place, 69% of them presenting positive PRA (panel reactive antibodies) (p=<0.05). Finally 24% of poly transfused patients presented anti-HLA antibodies (p=<0.05). CONCLUSIONS: During the 2 year of the study, 51 patients were transplanted, presenting only one of them anti-HLA antibodies before transplantation. This results clearly indicate that the immunization against HLA represents a barrier for transplantation access

Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial / Reflexologia podal no comprometimento dos pés de pessoas com diabetes mellitus tipo 2: ensaio randomizado / Reflexología podal en el comprometimiento de los pies de personas con diabetes mellitus tipo 2: ensayo aleatorio

AbstractObjective: to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus.Method: this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value <0.05).Results: participants who received the therapy showed better scores in some impairment indicators related to skin and hair (hair growth, elasticity/turgor, hydration, perspiration, texture and integrity of the skin/ skin peeling).Conclusion: the foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.

ResumoObjetivo:avaliar o efeito da reflexologia podal no comprometimento dos pés de pessoas com diabetes mellitus tipo 2.Método:trata-se de um ensaio clínico, randomizado, controlado e mascarado. A amostra foi composta por pessoas com diabetes mellitus tipo 2 que, após serem randomizadas em grupo Tratado (n=21) e Controle (n=24), receberam orientações de autocuidado com os pés. Ao Grupo Tratado também foram fornecidas 12 sessões de reflexologia podal. Foram mensurados os escores de comprometimento de indicadores relacionados à pele e pelos, circulação sanguínea, sensibilidade e temperatura tissular por meio do Instrumento para avaliação da integridade tissular dos pés de pessoas com diabetes mellitus. Aos dados foram aplicados os testes Qui-Quadrado, Exato de Fisher, Mann-Whitney e Análises de regressão, considerando-se nível de significância de 5% (Valor P<0,05).Resultados:os participantes que receberam a terapia apresentaram melhores escores de comprometimento em alguns indicadores relacionados à pele e pelos (crescimento de pelos, elasticidade/tugor, hidratação, transpiração, textura e integridade da pele/descamação cutânea).Conclusão:a reflexologia podal apresentou efeito benéfico sobre o comprometimento dos pés de pessoas com diabetes mellitus tipo 2, o que a torna uma terapia viável e que merece investimento. Este estudo foi registrado no Registro Brasileiro de Ensaios Clínicos - RBR-8zk8sz.

ResumenObjetivo:evaluar el efecto de la reflexología podal en el comprometimiento de los pies de personas con diabetes mellitus tipo 2.Método:se trata de un ensayo clínico, aleatorio, controlado y enmascarado. La muestra estuvo compuesta por personas con diabetes mellitus tipo 2 que, después de ser tratadas aleatoriamente en los grupos Tratado (n=21) y Control (n=24), recibieron orientaciones de autocuidado de los pies. También, al Grupo Tratado se le suministraron 12 sesiones de reflexología podal. Fueron medidos los puntajes de comprometimiento de indicadores relacionados a la piel y pelos, circulación sanguínea, sensibilidad y temperatura tisular por medio de instrumento para evaluación de la integridad del tejido de los pies de personas con diabetes mellitus. Los datos fueron sometidos a las pruebas Chi-cuadrado, Exacta de Fisher, Mann-Whitney y Análisis de regresión, considerando un nivel de significación de 5% (Valor p<0,05).Resultados:los participantes que recibieron la terapia presentaron mejores puntajes de comprometimiento en algunos indicadores relacionados a la piel y pelos (crecimiento de pelos, elasticidad/turgencia, hidratación, transpiración, textura e integridad de la piel/descamación cutánea).Conclusión:la reflexología podal presentó efecto benéfico sobre el comprometimiento de los pies de personas con diabetes mellitus tipo 2, lo que la torna una terapia viable y que merece inversiones. Este estudio fue registrado en el Registro Brasileño de Ensayos Clínicos - RBR-8zk8sz.

Effects of rhG-CSF Stimulation in vitro on the Adhesion and Polarization of Human CD4⁺T Lymphocytes / 中国实验血液学杂志

The adhesion and polarization of T lymphocytes involved in the adhesive interaction of lymphocyte function-associated antigen 1 (LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulation in vitro on the adhesion and polarization of CD4⁺ T cells of healthy human in peripheral blood. The peripheral blood mononuclear cells were collected from 12 healthy volunteers. The CD4⁺ T cells were sorted by miniMACS. The sorted CD4⁺ T cells were incubated with rhG-CSF for 24 h, then the adhesion and polarization of CD4⁺ T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by ELISA and inverted microscope. The results showed that the percentage of adhesion CD4⁺T cells in the experimental group (rhG-CSF acting on the healthy adult volunteers) (61.9 ± 5.9)% was lower than that in the control group (healthy adult volunteers without rhG-CSF stimulation) (68.3 ± 7.3)% (P < 0.05). The percentage of polarized CD4⁺T cells in the experimental group (24.3 ± 4.3)% was also lower than that in control group (47.1 ± 5.1)% (P < 0.05). It is concluded that the adhesion and polarization of CD4⁺T lymphocytes can be inhibited after rhG-CSF stimulation.

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

Galectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on different cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its effects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this effect is counteracted by the anti-Gal-8 autoantibodies. Given that Gal-8 can potentially interact with several glycoproteins, here we analyzed the β2 integrin Lymphocyte Function-Associated Antigen-1 (LFA-1), which is involved in leukocyte cell adhesion and immunological synapses. We show by GST-pull down assays that Gal-8 interacts with LFA-1 and this interaction is inhibited by anti-Gal-8 autoantibodies isolated from SLE patients. In cell adhesion assays, Gal-8 precluded the interaction of LFA-1 with its ligand Intracellular Adhesion Molecule-1 (ICAM-1). These results suggest that Gal-8 can exert immunosuppressive action not only by inducing apoptosis in activated T cells but also by negatively modulating the crucial function of LFA-1 in the immune system, while function-blocking autoantibodies counteract these effects.

CD16 expression is an independent prognostic factor for extranodal NK/T cell lymphoma of nasal type / 中华病理学杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic features of extranodal NK/T cell lymphoma, nasal type (ENKTCL-N), to explore the expression of NK cell-associated receptors in ENKTCL-N and the relationship with prognosis, and to establish a prognostic model.</p><p><b>METHODS</b>One hundred and twenty-six cases of ENKTCL-N were selected from the files of the Department of Pathology, West China Hospital of Sichuan University. The relevant clinical and follow-up data were collected, and the histopathology was reviewed. All specimens were stained immunohistochemically for CD16, ICAM-1 and LFA-1. RT-PCR was used to detect the expression of CD94, NKG2 and KIR. The relationship between the prognosis of ENKTCL-N, clinical features, histopathological characteristics and expression of these markers were also analyzed.</p><p><b>RESULTS</b>ENKTCL-N mainly occurred in middle-age and young patients (median age, 41 years). The male to female ratio was 3.2:1. Sites more commonly involved were the nose and upper aerodigestive tract whereas those for the non-nasal type were the skin and gut. Only six cases involved two or more extranodal sites. Most (86.5%, 109/126) of the patients were in clinical stages I/II. The tumors showed predominately medium-sized tumor cells and large-sized tumor cells accounted for only 9.5% (12/126). Coagulative necrosis was present in all cases. The expression rates of CD56, CD16, CD94, LFA-1 and ICAM-1 were 82.6% (95/115), 15.1% (19/126), 55.4% (41/74), 40.5% (51/126) and 0, respectively. The expression rate of NKG2 receptor was 90.5% (67/74) overall. NKG2 receptor expression was independent of CD94. The overall expression rate of KIR receptor was 33.8% (25/74) and KIR receptor restriction was not detected in 20.8% (5/24) of the cases. Follow-up data was available in all patients, with median and average survival time being 15 months and 20.2 months, respectively. Survival analysis showed that prognostic factors included the gender, age, disease type, extranodal involvement, stage, the expression of CD16, LFA-1 and CD94. Cox's proportional hazard regression analysis revealed four factors, age, involved site, stage and CD16 expression, were independent prognostic factors.</p><p><b>CONCLUSIONS</b>The age, disease type, stage and CD16 expression are independent prognostic factors. Establishment of a prognostic model based on the above four factors can be more accurate in the prognostication of ENKTCL-N. The differences in the clinical features, prognosis, and expression of NK cell-associated receptors are obvious between nasal NK-cell lymphoma and non-nasal NK-cell lymphoma.</p>

Extravasating Neutrophil-derived Microparticles Preserve Vascular Barrier Function in Inflamed Tissue

Emerging evidence suggests that gap formation and opening of the endothelial junctions during leukocyte extravasation is actively controlled to maintain the integrity of the vascular barrier. While the role for endothelial cells to this process has been well defined, it is not clear whether leukocytes are also actively contributing to endothelial barrier function. We have recently showed that extravasating leukocytes deposit microparticles on the subendothelium during the late stages of extravasation, which is LFA-1 dependent. Using multiphotonintravital microscopy (MP-IVM) of mouse cremaster muscle vessels in the current work, we show that microparticle formation and deposition maintains the integrity of the microvascular barrier during leukocyte extravasation. Inhibition of neutrophil-derived microparticle formation resulted in dramatically increased vascular leakage. These findings suggest that deposition of microparticles during neutrophil extravasation is essential for maintaining endothelial barrier function and may result in temporal difference between neutrophil extravasation and an increase in vascular leakage.

Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis / Expressão de RANTES, eotaxina-2, ICAM-1, LFA-1 e CCR-3 em pacientes com rinossinusite crônica associada à polipose nasossinusal

PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.

OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.

Frequência de imunofenótipos aberrantes em leucemias agudas: análise de 213 casos diagnosticados na Fundação Hemope / Frequency of aberrant immunophenotypes in acute leukemia: analysis of 213 cases diagnosed in Fundação Hemope

As leucemias agudas (LAs) são doenças clonais do tecido hematopoético caracterizadas por proliferação anômala de progenitores das diferentes linhagens. 0 diagnóstico das LAs se baseia em achados citomorfológicos, citoquimicos e imunofenotipicos em células da Medula Óssea (MO) e/ou Sangue Periférico (SP). Cerca de 30 a 50% das LMAs e LLAs, bem caracterizadas pelo imunofenótipo, exibem expressão de antigenos aberrantes e esta situação deve ser distinguida das leucemias bifenotipicas, que tem atualmente critérios de diagnóstico bem definidos. A detecção dos antígenos aberrantes não parece ter implicação prognóstica, mas é uma importante ferramenta para a detecção de doença residual mínima (DRM). 0 objetivo deste trabalho foi relatar a frequência de Fenótipos Aberrantes (FA) em LAs nos pacientes diagnosticados na Fundação Hemope, correlacionar este achado com a idade e identificar os antígenos aberrantes predominantes. 0 estudo contou com 213 pacientes de ambos os sexos e sem restric;:ao de faixa etária ou raça. A imunofenotipagem utilizou amostras de SP e/ou MO, sendo a análise realizada por citometria de fluxo multiparamétrica. Para as LMAs, LLAs BeLLAs T as frequências de FA encontradas foram de 47%, 40% e 52%, respectivamente. Os antígenos aberrantes predominantes foram CD? e CD56 para as LMAs e CD13 e CD33 para as LLAs. A frequência de antígenos aberrantes (45%) e a predominância de antígenos linfocitários T e NK na LMAs e de antígenos mielóides nas LLAs, condizem com a literatura. Por outro lado, o predomínio de FA entre os adultos parece sugerir mais uma caracteristica da amostra, onde esta faixa etária predominou, que uma caracteristica biológica das leucemias analisadas. Finalmente, este estudo, definindo melhor o perfil imunofenotipico de nossos pacientes, possibilita o uso deste conhecimento na avaliação de DRM.

Acute leukemias (AL) are clonal diseases of the hematopoietic tissue characterized by anomalous proliferation of precursors of different lineage. The diagnosis of AL is based on morphological, citochemical and immunophenotypical findings in cells of Bone Marrow (BM) and/or Peripheral Blood (PB). About 30 to 50% of AML and ALL, well-characterized by immunophenotype, display aberrant expression of antigens and this situation should be distinguished from biphenotipic leukemias, which are currently well-defined criteria for diagnosis. The detection of aberrant antigen does not seem to have prognostic implication, but it is an important tool for the detection of minimal residual disease (MRD). The objective of this study was to report the frequency of aberrant phenotypes (AP) at AL in patients diagnosticated by Funda9iio Hemope, correlate this finding with age and identify the predominant aberrant antigens. The study included 213 patients of both genders and without restriction of age or race. The immunophenotyping used samples of PB and/or BM, being the analysis by multiparametric flow cytometry. For AML, B-ALL and T-ALL the frequencies of FA found were 47%, 40% and 52% respectively. The predominant aberrant antigens for AML were CD7 and CD56 and for ALL were CD33 and CD13. The frequency of aberrant antigens (45%) and the predominance of lymphocyte T and NK antigens in AML and myeloid antigens in ALL, matches with the literature. Moreover, the prevalence of AP among adults, who are the predominant age group, seems to be more suggestive of a characteristic of the sample, than a biological feature of leukemias that were analyzed. Finally, this study, defines better the immunophenotypical profile of our patients and allows the use of this knowledge in the evaluation.

Effects of TNF-α on ICAM-1 and LFA-1 expression in peripheral blood mononuclear cells of children with febrile seizures / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of TNF-α on ICAM-1 and LFA-1 expression in peripheral blood mononuclear cells (PBMC) of children with febrile seizures (FS).</p><p><b>METHODS</b>Sixteen children with FS and 16 age- and gender-matched healthy children were enrolled. The samples of PBMC from FS children were randomized into two groups with or without TNF-α treatment (TNF-α concentration 1.0 ng/mL). PBMC were purified and cultured with a conventional method in vitro. The expression of ICAM-1 and LFA-1 in PBMC was determined by flow cytometry (FCM).</p><p><b>RESULTS</b>ICAM-1［(20±9)% vs (14±7)%)］and LFA-1［(43±16)% vs (30±16)%］expression in PBMC in the untreated FS group was significantly higher than that in the normal control group (P<0.05). Compared with the untreated FS group, the treatment with TNF-α remarkably increased the ICAM-1 expression［(27±11)%］(P<0.05). PBMC LFA-1 expression［(52±21)%］in the TNF-α-treated group was higher than that in the untreated FS group, although there were no statistical differences between the two groups.</p><p><b>CONCLUSIONS</b>TNF-α treatment may increase LFA-1 and ICAM-1 expression in PBMC of children with FS.</p>

Soluble intercellular adhesion molecule-1 and lymphocyte function associated antigen-1 in viral related chronic liver diseases

We attempted to assess the relationship between soluble intercellular adhesion molecules-I [sICAM-1] in serum and ascitic fluid and its counterpart ligand, lymphocyte function associated antigen-1 [LFA-1] on peripheral blood lymphocytes, accompanied by biochemical and haematological markers of disease activity in patients with viral related chronic liver disease [CLD] classified into Child-Pugh class A to C. Serum and ascitic fluid levels of sICAM using enzyme-linked immunosorbent assay and LFA-1 expression on peripheral lymphocytes using monoclonal antibodies by flow cytometry, were measured in 44 viral-related CLD patients, and 16 healthy controls. All patients were positive for HCV-RNA in their sera, with coexistence of HBV in 5 patients. According to standard criteria of Child-Pugh classification, patients were divided into 3 groups; Child A class [17 cases], B [16 cases] and C [11 cases]. Only 17 out of 44 patients, had ascitis complicating liver cirrhosis [6 from group B and all group C] and their ascitic fluid samples were tested for bacterial detection besides sICAM. Correlation analyses between studied parameters were performed. A significant gradual increase of serum sICAM-1 level was observed in all patients compared to the control, with highest values in Child C group. Serum sICAM exhibited significant direct correlations with prothrombin time [PT], ALT and LFA-1 expression on lymphocytes while inversely correlated with serum albumin and absolute lymphocytic counts. Concentration of sICAM-1 in the uninfected ascitic fluid of the studied cirrhotic patients was tremendously lower than that in serum. Statistically significant reduction of the% of LFA-1 expression on lymphocytes was noticed on comparing Child A group to the control followed by a gradual irrelevant increase with progressing Child grading. In chronic viral hepatitis, serum levels of sICAM-1 has a prognostic significance of the synthetic capacity of the liver, also it could be considered as an additional useful marker of necro-inflammatory activity subsequently, may be helpful, especially in patients in which liver biopsy is not possible. Conversely, measurement of sICAM in the uninfected ascitic fluid is unpredictable marker being present in trace amounts. The increased serum sICAM-1 concomitant with increased LFA-1 expression on peripheral lymphocytes with advancement of the disease can reflect the increased adhesion of these cells to their ligand on endothelial cells

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function-associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function-associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

Effects of yougui pill on phenotype change of thymic dendritic cells induced by glucocorticoid in mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the influence of glucocorticoid on phenotype of thymic dendritic cells in mice and to investigate the protective effect of Yougui Pill (YGP) on it.</p><p><b>METHODS</b>BALB/c mice allocated in the group A and B were treated respectively with 10 mg/kg hydrocortisone, alone and combined with 20.81 g/kg YGP. The control mice were treated with normal saline. The changes before and after treatment of I-A(d) and H-2K(d) antigen presentation molecules expression in CD11c(+) and CD45(+) thymic dendritic cells of mice were analyzed by flow cytometry assay, and the expression of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) mRNA in thymocytes were determined by RT-PCR as well.</p><p><b>RESULTS</b>The percentage of I-A(d+) and H-2K(d+) in CD11c(+) in Group A after treatment was 46.77 +/- 4.32% and 64.34 +/- 7.69% respectively, as compared with those in the control group (65.81 +/- 7.69% and 31.88 +/- 5.01%), the percentage of I-A(d+) was lower and that of H-2K(d+) was higher significantly (all P <0.01). Meantime, the expression of ICAM-1 and LFA-1 in thymocyte in Group A (30.11 +/- 2.51% and 30.40 +/- 3.77%) was significantly lower than that in the control group (46.35 +/- 3.34% and 47.28 +/- 2.91%) respectively (P <0.01). Changes in Group B showed that treated by hydrocortisone in combination with YGP, the above-mentioned hydrocortisone-induced changes could be obviously reversed, the outcome of CD11c(+) I-A(d+) was 54.19 +/- 5.08%, ICAM-1 33.97 +/- 2.04% and LFA-1 34.80 +/- 2.92%, the difference between the two treated groups in these indexes all showed statistical significance (P <0.05).</p><p><b>CONCLUSION</b>Glucocorticoidcan inhibit the expression of major histocompatibility complex class II antigen molecule, but promote the expression of major histocompatibility complex class I in CD11c(+) and CD45(+) dendritic cells, down-regulate ICAM-1 and LFA-1 transcription, while the tonifying yang recipe, YGP, has a dominant protective effect against the above actions of glucocorticoid.</p>

An update on beta2 integrin LFA-1 and ligand ICAM-1 signaling / 中国实验血液学杂志

LFA-1 and ICAM-1 mediate a bi-directional signaling across the cell membrane which is essential for biological functions of lymphocyte, including exudation, activation, adhesion, immunosurveillance as well as immuno-logical synapse formation. The signal transducing is a dynamic process and dependent on the binding capacity between LFA-1 and ICAM-1. The affinity and the avidity of LFA-1 are two major regulation forms in this process. Phosphorylation of LFA-1 and cytoskeleton protein talin 1 play a critical role in signal transducing. In biology of lymphocyte, LFA-1 and ICAM-1 interaction forms the co-stimulatory signal to promote activation, proliferation and division. In this article the regulation of binding capacity between LFA-1 and ICAM-1, the regulation of LFA-1 subunit phosphorylation, the role of talin1 in signaling transduction of LFA-1 and ICAM-1, the synergic stimulatory signaling of LPA-1 and ICAM-1 were reviewed.

LFA-1 and VLA-4 involved in vasoendothelial adhesion and transendothelial migration of human high proliferative potential endothelial progenitor cells / 中国实验血液学杂志

To investigate whether lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) are involved in vasoendothelial adhesion and transendothelial migration of high proliferative potential endothelial progenitor cells (HPP-EPCs), flow cytometry was used to analyze the expression of integrin beta1 and beta2, the expression of intercellular adhesion molecule (ICAM-1, 2) and vascular cell adhesion molecule (VCAM-1) in mouse bone marrow endothelial cells (mBMECs). The adhesion and transmigration through endothelial cells of the HPP-EPCs blocked by functional grade neutralizing antibodies of VLA-4 and LFA-1 were studied in vitro. The results revealed that HPP-EPCs were positive for CD11a and CD49d in HPP-EPCs. The expression of ICAM-1and VCAM-1 of mBMECs increased after activated by IL-1beta and TNF-alpha. The results of adhesion in vitro revealed that the numbers of the adhered and migrated cells in the CD11a antibody group, in the CD49d antibody group and in the combinational antibody group were less than those in the isotype control antibody group. Furthermore, the number of adhered and migrated cells in the combinational antibody group was less than that in the CD11a or the CD49d antibody group (p < 0.05). It is concluded that both LFA-1 and VLA-4 are involved in vasoendothelial adhesion and transendothelial migration of HPP-EPCs.

Beneficial effects of hydrocortisone in induced acute pancreatitis of rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Little is known of the effects of hydrocortisone on cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and its counterreceptors (LFA-1, Mac-1) in acute pancreatitis (AP). We investigated the effects of prior treatment with hydrocortisone on the production of ICAM-1 and its counterreceptors (LFA-1 and Mac-1) in AP of rats to clarify the effect of hydrocortisone on induced acute pancreatitis.</p><p><b>METHODS</b>Acute pancreatitis was induced by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ligation of pancreatic duct. Before induction of acute pancreatitis, rats were treated with hydrocortisone (n = 20) or 0.9% saline (n = 20). Blood and specimens from pancreas and lung were obtained from 5 rats from each treatment euthanized at 1 hour or 3 hours, 6 hours, 12 hours. Expression of ICAM-1 was assessed by immunohistochemistry and Western blot analysis of pancreas and lungs. The expression of LFA-1 and Mac-1 on neutrophils was detected by flow cytometer. The therapeutic effect of hydrocortisone was assessed from injuries to pancreas and lung.</p><p><b>RESULTS</b>ICAM-1 expression in the pancreas of hydrocortisone group was significantly less than in control group at 3 hours and 6 hours. In the lungs of hydrocortisone group, ICAM-1 expression was significantly less than in control group at 3 hours, 6 hours and 12 hours. The expression of LFA-1 and Mac-1 on neutrophils in blood increased significantly in control group over hydrocortisone group. Increased expression of ICAM-1, LFA-1 and Mac-1 preceded leukocyte infiltration. Compared to untreated animals with acute pancreatitis, rats pretreated with hydrocortisone had significantly reduced histological lung injury and output of ascitic fluid.</p><p><b>CONCLUSIONS</b>Prior treatment with hydrocortisone before the induction of acute pancreatitis ameliorates pulmonary injury and the output of ascitic fluid and reduces the expression of ICAM-1 and its counterreceptors (LFA-1, Mac-1) in acute pancreatitis.</p>

The impact of rhG-CSF mobilization on migration and adhesive function of CD4+ T cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the impact of mobilization with recombinant human granulocyte colony stimulated factor (rhG-CSF) on the migration and adhesive function and their related signal mechanism mediated by the CXCR4 and lymphocyte function antigen-1 (LFA-1) molecules on the surfaces of CD4(+) T cells.</p><p><b>METHODS</b>Before and at day 5 on rhG-CSF mobilization, the expression rates of CXCR4 and LFA-1 (CD11a) on CD4(+) T cells in the peripheral blood were detected by tricolor fluorescence labeling, and the migration and adhesive activities of CD4(+) T cells to stroma cell-derived factor 1 alpha (SDF-1 alpha) and intercellular adhesion molecule-1 (ICAM-1) were also tested.</p><p><b>RESULTS</b>The expression of CXCR4 on CD4(+) T lymphocytes was (84.58 +/- 20.31)% before mobilization and (81.23 +/- 22.46)% at day 5 on mobilization. The expression of LFA-1 on CD4(+) T lymphocytes before and at day 5 on mobilization was 100%. There was no significant difference in the expression CXCR-4 and LFA-1 on CD4(+) T lymphocytes whether mobilization (P > 0.05). SDF-1 alpha induced 4 hours' CD4(+) T cells migration didn't change markedly before and after mobilization \[(28.5 +/- 10.3)% vs (31.2 +/- 8.9)%\] (P > 0.05). The adhesive activity of CD4(+) T cells to ICAM-1 was decreased from (85.59 +/- 14.21)% to (61.45 +/- 15.07)% after mobilization (P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of CXCR4 and LFA-1 on CD4(+) T lymphocytes didn't change markedly during rhG-CSF mobilization, but the adhesive activity of CD4(+) T cells to ICAM-1 was frustrated after that.</p>

Cytoplasmic Domain of Intercellular Adhesion Molecule-1(ICAM-1)is Important for the ICAM-1 Mediated Membrane Projection of Endothelial Cells / 대한해부학회지

Intercellular adhesion molecule-1 (ICAM-1)has been shown to enhance leukocyte adhesion, thereby inducing migration through blood endothelial cells. However, the molecular event during the process of adhesion is largely unknown. To examine the role of ICAM-1 cytoplasmic domain in SDF-1 alpha-induced T lymphocyte migration and adhesion, mutant human ICAM-1 molecules were expressed in COS-7 cell line. COS-7 cells expressing ICAM-1_GFP mutant without alpha-actinin revealed no association with the actin cytoskeleton, while wild-type ICAM-showed clear association with the actin, as observed by confocal microscopy, suggesting that actinin binding motif in the cytoplasmic domain of ICAM-1 is important for the proper localization of ICAM-1 on the cell membrane. However, based on adhesion assay, we found that the cytoplasmic domain of ICAM-1 is not essential for the binding of lymphocytes which were activated by SDF-1alpha. On the other hand, ICAM-1-mediated receptor-ligand clustering event was significantly inhibited in the cells expressing ICAM-1 mutants without alpha-actinin or whole cytoplasmic domain. Taken together, these results suggest that ICAM-1 cytoplasmic domain is not essential for the adhesion but important for the ligand-receptor-mediated membrane projection of endothelial cells before trans-endothelial migration of lymphocytes.