A Study On The Molecular Mechanism Of Heterogeneous Apoptosis Of Lymphocytes, Eosinophils, And Neutrophils From Peripheral Blood Of Asthmatic Patients

Objectives To observe different responsiveness of lymphocytes,eosinophils,and neutrophils from peripheral blood of asthmatic patients to dexamethasone and montelukast-induced apoptosis, explore the rolesof Fas antigen and caspase-3 in the heterogeneity of cell apoptosis. Methods Lymphocytes,eosinophils,and neutrophils were isolated from peripheral blood of 18 subjects of asthmatic patients diagnosed firstly and not treated .In vitro cells were co-incubated with dexamethasone and leukotriene receptor antagonist ,montelukast.Cell apoptosis rates and Fas expression rates were examined by flowcytometry whereas caspase-3 levels in these cells were detected by ELISA. Results Lymphocytes,eosinophils,and neutrophils underwent apoptosis and expressed low levels of Fas antigen spontaneously with constitutive caspase-3 activity detected.Both Dexamethasone and montelukast markedly induced apoptosis and Fas expression of lymphocytes and eosinophils. The apoptosis increased three times induced by dexamethasone markedly,and the effects of apoptpsis induced by montelukast are strong than that of dexamethasone. Forthermore,activity of caspase-3 in lymphocytes and eosinophils increasing induced by dexamethasone and montelukast . Dexamethasone, however ,can not induce apoptpsis of neutrophils ,and Fas antigen expression and caspase-3 levels in neutrophils were not markedly altered ,too. Montelukast,not dexamethasone,induced neutrophils apoptosis,but neither the level of caspase-3 nor the expression of Fas antigen was altered significantly. Conclusions In asthmatic inflammatory modulating andeffective cells,neutrophils is distinct from lymphocytes and eosinophils in profile of apoptosis induced by glucocosteroid and leukotriene receptor antagonist.The signal pathway contributing neutrophil apoptosis heterogeneity may involve deficient caspase cascade or Fas/FasL .