Mann Bhupinder S, Chung Kian Fan
National Heart & Lung Institute, Imperial College & Royal Brompton Hospital London, UK.
Respir Res. 2006 Apr 6;7(1):59. doi: 10.1186/1465-9921-7-59.
Neutrophils are increased in the airways and in induced sputum of severe asthma patients. We determined the expression of activation markers from circulating neutrophils in severe asthma, and their supressibility by corticosteroids.
We compared blood neutrophils from mild, moderate-to-severe and severe steroid-dependent asthma, and non-asthmatics (n = 10 each). We examined the effect of adding or increasing oral prednisolone (30 mg/day;1 week).
Flow cytometric expression of CD35 and CD11b, but not of CD62L or CD18, was increased in severe asthma. F-met-leu-phe increased CD11b, CD35 and CD18 and decreased CD62L expression in all groups, with a greater CD35 increase in severe asthma. In severe steroid-dependent asthma, an increase in prednisolone dose had no effect on neutrophil markers particularly CD62L, but reduced CD11b and CD62L on eosinophils. Phorbol myristate acetate-stimulated oxidative burst and IL-8 release by IL-1beta, lipopolysaccharide and GM-CSF in whole blood from mild but not severe asthmatics were inhibited after prednisolone. There were no differences in myeloperoxidase or neutrophil elastase release from purified neutrophils.
Because blood neutrophils in severe asthma are activated and are not inhibited by oral corticosteroids, they may be important in the pathogenesis of severe asthma.
在重度哮喘患者的气道和诱导痰中，中性粒细胞数量增加。我们测定了重度哮喘患者循环中性粒细胞中活化标志物的表达情况，以及它们对皮质类固醇的敏感性。
我们比较了轻度、中度至重度和重度激素依赖型哮喘患者以及非哮喘患者（每组10人）的血液中性粒细胞。我们研究了添加或增加口服泼尼松龙（30毫克/天；1周）的效果。
重度哮喘患者中，CD35和CD11b的流式细胞术表达增加，但CD62L或CD18的表达未增加。在所有组中，F-甲硫氨酰-亮氨酰-苯丙氨酸增加了CD11b、CD35和CD18的表达，并降低了CD62L的表达，重度哮喘患者中CD35的增加更为明显。在重度激素依赖型哮喘中，增加泼尼松龙剂量对中性粒细胞标志物尤其是CD62L没有影响，但降低了嗜酸性粒细胞上的CD11b和CD62L。泼尼松龙治疗后，轻度而非重度哮喘患者全血中佛波酯肉豆蔻酸酯乙酸盐刺激的氧化爆发以及IL-1β、脂多糖和GM-CSF诱导的IL-8释放受到抑制。纯化中性粒细胞释放的髓过氧化物酶或中性粒细胞弹性蛋白酶没有差异。
由于重度哮喘患者的血液中性粒细胞被激活且不受口服皮质类固醇抑制，它们可能在重度哮喘的发病机制中起重要作用。
