The Expression Of CXCR3 On Peripheral Blood T Cell In Patients With COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a cause of chronic morbidity and morbility throughout the world. Many people suffer from COPD, and eventually die from the disease and its complications. Currently, COPD is the fourth leading cause of death in the world,and further increases in its prevalence and montality can be predicted in the coming decades. The pathogenesis of molecular and cellular mechanisms of COPD are not yet fully understood. Inflammatory cells including neutrophils, macrophages and lymphocytes are involved in COPD. The roles of lymphocytes played in the pathogenesis of COPD is not yet clear. Chemokines are a class of small molecules widely participating in inflammatory response, inducing cell directional migration to specific sites and generate local immune response through a combination of chemokine receptors, which may be the most important factor of inflammation. Chemokine receptor 3 (CXCR3) mainly expresses on the surface of T lymphocytes and play an important role in the migration of T lymphocytes to the inflammatory sites.Study on this item will help to clarify the mechanism of lymphocytes in the pathogenesis of COPD.ObjectiveOne aim was to investigate the role of CXCR3 expression on peripheral blood T cells in the pathogenesis of COPD.And discuss whether aminophylline and corticosteroids, which are commonly used in the treatment of COPD, can affect the expression of CXCR3 on T cells.MethodsSubjects were classed into normal control group(n=14), COPD acute exacerbation group(n=20) and COPD stable group(n=17). Venous bloods were taken from AECOPD patients at their first admission,and the second time, take venous bloods again when cough, sputum, shortness of breath and other symptoms were stabilized after about 7～24 days, an average of 14.1±4.6 days of hospital treatment. Venous bloods of stable COPD patients and control group were also studied. Peripheral blood mononuclear cells (PBMCs) were separated and labeled with CXCR3 antibody. The expression of CXCR3 on T cells of three groups were detected by flow cytometry.Peripheral blood mononuclear cells (PBMCs) were isolated from stable COPD patients who have not administrated with aminophylline and budesonide within 2 months. Cells were treated with normal saline, aminophylline (1.6μg/ml,16μg/ml) and budesonide (three concentration gradient 0.1nmol/l, 10nmol/l, 1000nmol/l), incubated at 37℃CO2 incubators for 72 hours. Expressions of CXCR3 on T cell were then detected by flow cytometry.ResultsThe expression of CXCR3 on T cells in patients with COPD. (1) There were no detectable differences in the percentage of CD4+and CD8+cells in total T cells in these groups, the same result was found after the treatment of AECOPD (P＞0.05). (2) The percentage of T lymphocytes expressing CXCR3 was lower in subjects with acute exacerbation of COPD than stable COPD and healthy controls (P< 0.05), higher level of lymphocytes expressing CXCR3 was observed in stable COPD than controls (P< 0.05). No difference of the MFI for CXCR3 on CD4+,CD8+cells was observed (P>0.05). (3) After treatment, CD4+CXCR3+cells in the total CD4+ cells,CD8+CXCR3+cells in the total CD8+cells and the MFI for CXCR3 on CD4+,CD8+cells were markedly decreased in AECOPD patients (P< 0.05).(4) Correlation analysis. There was no correlationship between the expression of CXCR3 on CD4+and CD8+cells and FEV1 percentage of predicted in patients with COPD.The effect of aminophylline and budesonide treatment on the expression of CXCR3 on T cells in patients with COPD. (1) Aminophylline group. The percentage of CD8+ CXCR3+T cells in the total of CD8+T cells.1.6μg/ml,16μg/ml aminophylline group had a tendency to decrease as compared with control group, but there was no significant difference (P>0.05).The same result was found between these different concentration of aminophylline groups (P> 0.05). The MFI for CXCR3 on CD8+cells in 1.6μg/ml,16μg/ml aminophylline groups were markedly decreased compared with control group (P< 0.05). There were no significant differences of the percentage of CD4+CXCR3+T cells in the total of CD4+T cells and the MFI for CXCR3 on CD4+cells in these groups (P>0.05). (2) Budesonide groups. The percentage of CD8+CXCR3+T cells in the total of CD8+T cells was significantly decreased in 0.1nmol/l, 10nmol/l, 1000nmol/l budesonide groups compared with control group (P< 0.05), the percentage in 1000nmol/l budesonide group was significantly declined compared with 0.1nmol/l budesonide group (P<0.05). The MFI for CXCR3 on CD8+cells was significantly decreased in 0.1nmol/l, 10nmol/l, 1000nmol/l budesonide groups as compared with control group (P< 0.05). No significance was observed among these budesonide groups (P>0.05). Compared with control group, the percentage of CD4+CXCR3+T cells in the total of CD4+T cells among 0.1nmol/l, 10nmol/l, 1000nmol/l budesonide groups had a tendency to decrease, but there was no significant difference (P>0.05). The MFI for CXCR3 on CD4+cells was significantly decreased in 10nmol/l, 1000nmol/l budesonide groups compared with control group (P< 0.05)Conclusions Quantitation changes in CD4+or CD8+T lymphocyte subsets and imbalance of CD4+T/CD8+T lymphocyte ratio did not occur in COPD patients.The overexpression of CXCR3 on T lymphocyte may be related with chronic inflammation in COPD.The overexpression of CXCR3 on T lymphocyte was not related to the severity of disease.Low or conventional dose of aminophylline treatment did not affect the percentage of CD8+CXCR3+T cells in the total of CD8+T cells, but weaken the ability of expression of CXCR3 on CD8+T lymphocyte.Budesonide, a glucocorticoid, decreased the expression intensity of CXCR3 on CD8+T lymphocyte.