Human CD14 mediates recognition and phagocytosis of apoptotic cells

Human CD14 mediates recognition and phagocytosis of apoptotic cells
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DOI:
10.1038/33169
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发表时间:
1998-04-02
期刊:
影响因子:
64.8
通讯作者:
Gregory, CD
Gregory, CD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Devitt, A;Moffatt, OD;Gregory, CD

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经历程序性细胞死亡(凋亡)的细胞在体内被吞噬细胞快速清除,而不引起炎症(1),这里我们表明,人类巨噬细胞表面的糖基磷脂酰肌醇连接的质膜糖蛋白 CD14 (参考文献 2, 3) 对于凋亡细胞的识别和清除很重要,CD14 还可以作为结合细菌脂多糖 (LPS) 的受体,引发炎症反应(4),LPS 过度刺激 CD14 可导致致命的中毒性休克综合征(5,6)。在这里,我们表明凋亡细胞与 CD14 相互作用,引发凋亡细胞的吞噬作用。这种相互作用取决于 CD14 的一个区域,该区域与已知结合 LPS 的区域相同或至少密切相关。然而,凋亡细胞与 LPS 不同,不会引起巨噬细胞释放促炎细胞因子。这些结果表明,凋亡细胞的清除是由与“非自身”成分相互作用的受体介导的。 (LPS) 和“自身”成分(凋亡细胞)产生不同的巨噬细胞反应。
Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by phagocytes without inducing inflammation(1), Here we show that the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 (refs 2, 3) on the surface of human macrophages is important for the recognition and clearance of apoptotic cells, CD14 can also act as a receptor that binds bacterial lipopolysaccharide (LPS), triggering inflammatory responses(4), Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome(5,6). Here we show that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells, This interaction depends on a region of CD14 that is identical to, or at least closely associated with, a region known to bind LPS, However, apoptotic cells, unlike LPS, do not provoke the release of pro-inflammatory cytokines from macrophages, These results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with 'non-self' components (LPS) and 'self' components (apoptotic cells) produce distinct macrophage responses.