Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF
Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF
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DOI：
10.1172/jci1112
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发表时间：
1998-02-15
影响因子：
15.9
通讯作者：
Henson, PM
中科院分区：
文献类型：
--
作者：
Fadok, VA;Bratton, DL;Henson, PM
体内细胞凋亡几乎不可避免地伴随着邻近吞噬细胞的快速摄取，这是组织重塑、免疫应答调节、炎症消退的关键过程。巨噬细胞对凋亡细胞的吞噬作用被认为是一个安静的过程，它确实导致炎症介质的产生。（与免疫球蛋白G调理的凋亡细胞相反）主动抑制白细胞介素（IL）-1 β、IL-8、IL-10、粒细胞巨噬细胞集落刺激因子和肿瘤坏死因子-α的产生，以及白三烯C-4和血栓素B2。相反，转化生长因子（TGF）-β 1、前列腺素E2和血小板活化因子（PAF）的产生增加。后者似乎参与了促炎细胞因子产生的抑制，因为外源性TGF-β 1、前列腺素E2或PAF的加入导致了脂多糖刺激的细胞因子产生的抑制。此外，抗TGF-β抗体、吲哚美辛或PAF受体拮抗剂恢复了吞噬凋亡细胞的脂多糖刺激的巨噬细胞中的细胞因子产生。这些结果表明，凋亡细胞的结合和/或吞噬诱导了人巨噬细胞的活性抑制或抑制特性。因此，很可能炎症的消退不仅取决于凋亡细胞的去除，而且取决于炎症介质产生的主动抑制。任何一种疾病都可能导致慢性炎症性疾病。
Apoptosis in vivo is followed almost inevitably by rapid up-take into adjacent phagocytic cells, a critical process in tissue remodeling, regulation of the immune response, car resolution of inflammation. Phagocytosis of apoptotic cells by macrophages has been suggested to be a quiet process that does Plot lead to production of inflammatory mediators, Here we show that phagocytosis of apoptotic neutrophils (in contrast to immunoglobulin G-opsonized apoptotic cells) actively inhibited the production of interleukin (IL)-1 beta, IL-8, IL-10, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor-alpha, as well as leukotriene C-4 and thromboxane B2, by human monocyte-derived macrophages. In contrast, production of transforming growth factor (TGF)-beta 1, prostaglandin E2, and platelet-activating factor (PAF) was increased, The latter appeared to be involved in the inhibition of proinflammatory cytokine production because addition of exogenous TGF-beta 1, prostaglandin E2, or PAF resulted in inhibition of lipopolysaccharide-stimulated cytokine production. Furthermore, anti-TGF-beta antibody, indomethacin, or PAF receptor antagonists restored cytokine production in lipopolysaccharide-stimulated macrophages that had phagocytosed apoptotic cells, These results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages. Therefore, it is likely that resolution of inflammation depends not only on the removal of apoptotic cells but on active suppression of inflammatory mediator production, Disorders in either could result in chronic inflammatory diseases.