嗜酸细胞凋亡在激素抵抗型哮喘中的意义

目的 观察激素抵抗型（ＳＲ）哮喘是否存在嗜酸细胞（ＥＯＳ）凋亡功能的异常及促炎症细胞因子白细胞介素５（ＩＬ－５）和粒－巨细胞集落刺激因子（ＧＭ－ＣＳＦ）的调节作用。方法 分离ＳＲ（１５例）、激素敏感型（ＳＳ，３０例）两组哮喘患外周血单个核细胞（ＰＢＭＣＳ）及ＥＯＳ，体外培养后测定：（Ｆ１）ＰＢＭＣＳ在糖皮质激素处理前、后和细胞因子的能力；（２）自发的或糖皮质激素诱导的或用ＰＢＭＣＳ培养上液处理后

Effect of eosinophil apoptosis on glucocorticoid-resistant asthma

OBJECTIVE: To investigate the function of eosinophil apoptosis and regulation of glucocortico steroids on IL-5 and GM-CSF expression in peripheral blood mononuclear cells (PBMCs) in glucocorticoid-resistant asthmatic patients. METHODS: Eosinophils (EOS) and PBMCs isolated from glucocorticoid-sensitive (SS, 15 cases) and resistant (SR, 30 cases) asthmatic subjects were cultured and treated with dexamethasone (DXM) in vitro. Concentrations of IL-5 and GM-CSF were determined by ELISA in the supernatants recovered in sham and DXM treated cells. The rates of EOS apoptosis and Fas antigen expression were documented via flow cytometer in sham, DXM treated and PBMC supernatant treated groups respectively. RESULTS: There were no statistical significant differences of the concentrations of both IL-5 and GM-CSF in sham cultured PBMC supernatants between SS and SR groups (196 +/- 68) micrograms/L vs. (235 +/- 98) micrograms/L IL-5 (P > 0.05), (325 +/- 110) micrograms/L vs. (356 +/- 131) micrograms/L GM-CSF (P > 0.05); SS versus SR groups, respectively]. There were statistically significant decreases in both IL-5 and GM-CSF after DXM exposure in SS group (196 +/- 68) micrograms/L vs. (147 +/- 62) micrograms/L IL-5 (P < 0.01); (325 +/- 110) micrograms/L vs. (270 +/- 97) micrograms/L GM-CSF (P < 0.01)]. In contrast, there were no significant differences in both IL-5 and GM-CSF after DXM exposure in SR group. Baseline rates of both EOS apoptosis and Fas antigen expression were statistically significant different between SS and SR groups (67 +/- 21)% vs. (33 +/- 17)% the rate of EOS apoptosis (P < 0.001); (54 +/- 23)% vs. (27 +/- 15)% the rate of Fas antigen expression (P < 0.001), SS versus SR groups, respectively]. A dramatic increase in EOS apoptosis after DXM exposure was observed in SS group (67 +/- 21)% vs. (89 +/- 20)% (P < 0.01), baseline vs. DXM exposure, respectively], but there was no significant change in Fas antigen expression. There were no significant changes in both EOS apoptosis and Fas antigen expression in SR group after DXM exposure. CONCLUSIONS: These data suggest that EOS compromised apoptosis might exist and could not be affected by glucocorticoid induction in SR asthma. On the other hand, Th2 cytokine over-expression could not be inhibited by glucocorticoid in SR group in vitro.