Fas/CD95-Induced Chemokines Can Serve as %26quot;Find-Me%26quot; Signals for Apoptotic Cells

作者：Cullen Sean P; Henry Conor M; Kearney Conor J; Logue Susan E; Feoktistova Maria; Tynan Graham A; Lavelle Ed C; Leverkus Martin; Martin Seamus J

来源：Molecular Cell, 2013, 49(6): 1034-1048.

DOI：10.1016/j.molcel.2013.01.025

Apoptosis is commonly thought to represent an immunologically silent or even anti-inflammatory mode of cell death, resulting in cell clearance in the absence of explicit activation of the immune system. However, here we show that Fas/CD95-induced apoptosis is associated with the production of an array of cytokines and chemokines, including IL-6, IL-8, CXCL1, MCP-1, and GMCSF. Fas-induced production of MCP-1 and IL-8 promoted chemotaxis of phagocytes toward apoptotic cells, suggesting that these factors serve as %26quot;find-me%26quot; signals in this context. We also show that RIPK1 and IAPs are required for optimal production of cytokines and chemokines in response to Fas receptor stimulation. Consequently, a synthetic IAP antagonist potently suppressed Fas-dependent expression of multiple proinflammatory mediators and inhibited Fas-induced chemotaxis. Thus, in addition to provoking apoptosis, Fas receptor stimulation can trigger the secretion of chemotactic factors and other immunologically active proteins that can influence immune responsiveness toward dying cells.

• 出版日期2013-3-28