GRANULOCYTE APOPTOSIS AND THE CONTROL OF INFLAMMATION
GRANULOCYTE APOPTOSIS AND THE CONTROL OF INFLAMMATION
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DOI：
10.1098/rstb.1994.0113
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发表时间：
1994-08-30
期刊：
影响因子：
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通讯作者：
MEAGHER, LC
中科院分区：
文献类型：
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作者：
HASLETT, C;SAVILL, JS;MEAGHER, LC
我们描述了一种可用于从发炎组织中清除外渗粒细胞的新途径，从而老化的粒细胞经历细胞凋亡，这也可以在发炎部位看到，细胞凋亡代表粒细胞的命运，通过多种机制往往会限制炎症组织损伤并促进消退而不是炎症的进展：（i）细胞凋亡负责巨噬细胞识别具有完整细胞膜的衰老中性粒细胞，细胞膜排除活体染料并保留其潜在的组织毒性颗粒内容物； (ii) 凋亡的中性粒细胞在有意的外部刺激下失去分泌颗粒酶的能力； (iii) 巨噬细胞对凋亡的中性粒细胞具有巨大的吞噬能力，可快速吞噬并降解，而不释放中性粒细胞内容物； (iv)巨噬细胞利用一种新颖的吞噬识别机制，在凋亡中性粒细胞的吞噬过程中不能触发促炎巨噬细胞介质的释放。识别机制的初步表征涉及巨噬细胞表面的整合素 α v Beta-3（玻连蛋白受体）和 CD36（血小板反应蛋白受体）。巨噬细胞对凋亡中性粒细胞的吞噬作用很大程度上受微环境 pH 值和阳离子分子存在的影响。此外，它可以被外部细胞因子和细胞内第二信使系统特异性调节。通过控制中性粒细胞和嗜酸性粒细胞的功能寿命以及随后巨噬细胞的清除，粒细胞凋亡及其受外部介质调节的潜力，可能在炎症部位粒细胞“组织负荷”的控制中发挥关键的动态作用。进一步阐明粒细胞凋亡的机制和控制可能会给炎症的病理生理学带来新的启示，并提出治疗炎症性疾病的新方法。
We have described a novel pathway available for the clearance of extravasated granulocytes from inflamed tissues whereby aging granulocytes undergo apoptosis, which may also be seen at inflamed sites, apoptosis represents a granulocyte fate which by a number of mechanisms would tend to limit inflammatory tissue injury and promote resolution rather than progression of inflammation: (i) apoptosis is responsible for macrophage recognition of senescent neutrophils with intact cell membranes which exclude vital dyes and retain their potentially histotoxic granule contents; (ii) the apoptotic neutrophil loses its ability to secrete granule enzymes on deliberate external stimulation; (iii) the macrophage possesses a hugh phagocytic capacity for apoptotic neutrophils which it rapidly ingests and degrades without disgorging neutrophil contents; and (iv) the macrophage utilizes a novel phagocytic recognition mechanism which fails to trigger the release of pro-inflammatory macrophage mediators during the phagocytosis of apoptotic neutrophils. Preliminary characterization of the recognition mechanism implicates the integrin alpha v Beta-3 (vitronectin receptor) and CD36 (thrombospondin receptor) on the macrophage surface. Macrophage phagocytosis of apoptotic neutrophils is greatly influenced by the microenvironmental pH and by the presence of cationic molecules. Moreover, it can be specifically modulated by external cytokines and intracellular second messenger systems. By controlling the functional longevity of neutrophil and eosinophil granulocytes and their subsequent removal by macrophages, granulcoyte apoptosis, with its potential for modulation by external mediators, is likely to play a key dynamic role in the control of the 'tissue load' of granulocytes at inflamed sites. Further elucidation of the mechanisms and control of apoptosis in granulocytes is likely to shed new light on the pathophysiology of inflammation and suggest new approaches to the therapy of inflammatory diseases.