A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: A homeostatic mechanism in inflammation
A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: A homeostatic mechanism in inflammation
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DOI：
10.1016/s1074-7613(00)80278-2
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发表时间：
1996-12-01
期刊：
影响因子：
32.4
通讯作者：
Mayadas, TN
中科院分区：
文献类型：
--
作者：
Coxon, A;Rieu, P;Mayadas, TN
在选择性缺乏 CD11b/CD18 的小鼠中，β2 整合素、趋化剂诱导的白细胞在体内对微血管内皮的粘附减少。矛盾的是，巯基乙酸诱导的中性粒细胞在腹腔内的积累增加，并且与外渗细胞凋亡的显着延迟相关。外渗细胞几乎没有中性粒细胞吞噬作用，氧自由基生成减少，这可能导致观察到的细胞凋亡缺陷，这得到了我们的体外研究的支持，其中人中性粒细胞对调理颗粒的吞噬作用迅速诱导细胞凋亡，可以用 CD11b/CD18 抗体阻断，活性氧是该过程中的细胞内链接：在用黄素蛋白抑制剂二亚苯基碘和慢性肉芽肿病患者的中性粒细胞，这些患者缺乏 NADPH 氧化酶。因此，CD11b/CD18 通过加速外渗中性粒细胞的程序性消除，在炎症中发挥着一种新颖且未被怀疑的稳态作用。
In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant-induced leukocyte adhesion to microvascular endothelium in vivo was reduced. Paradoxically, thioglycollate-induced neutrophil accumulation in the peritoneal cavity was increased and was associated with a significant delay in apoptosis of extravasated cells. The extravasated cells had a near absence of neutrophil phagocytosis and a reduction in oxygen free radical generation, which may contribute to the observed defect in apoptosis, This is supported by our in vitro studies, in which phagocytosis of opsonized particles by human neutrophils rapidly induced apoptosis that could be blocked with CD11b/CD18 antibodies, Reactive oxygen species are the intracellular link in this process: phagocytosis-induced apoptosis was blocked both in neutrophils treated with the flavoprotein inhibitor diphenylene iodonium and in neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase. Thus, CD11b/CD18 plays a novel and unsuspected homeostatic role in inflammation by accelerating the programmed elimination of extravasated neutrophils.