Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor

作者：Nakahashi Oda Chigusa; Tahara Hanaoka Satoko; Shoji Masamichi; Okoshi Yasushi; Nakano Yokomizo Takako; Ohkohchi Nobuhiro; Yasui Teruhito; Kikutani Hitoshi; Honda Shin ichiro; Shibuya Kazuko; Nagata Shigekazu; Shibuya Akira^*

来源：Journal of Experimental Medicine, 2012, 209(8): 1493-1503.

DOI：10.1084/jem.20120096

When a cell undergoes apoptosis, phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. PS acts as an %26quot;eat-me%26quot; signal to direct phagocytes expressing PS receptors to engulf the apoptotic cell. We recently reported that the immunoreceptor CD300a, which is expressed on myeloid cells, is a PS receptor. We show that CD300a does not facilitate macrophage phagocytosis of apoptotic cells. Instead, CD300a delivers an inhibitory signal in mast cells to suppress production of LPS-induced inflammatory cytokines and chemokines. After cecal ligation and puncture (CLP), when a large number of cells undergo apoptosis in the peritoneal cavity, CD300a-deficient peritoneal mast cells produced more chemoattractant and recruited more neutrophils than did wild-type (WT) mast cells. As a result, CD300a-deficient mice showed increased neutrophil recruitment and improved bacterial clearance in the peritoneal cavity, and survived longer than WT mice. Antibody blockade of CD300a-PS interactions improved bacterial clearance and extended survival of WT mice subjected to CLP. These results indicated that CD300a is a nonphagocytic PS receptor that regulates mast cell inflammatory responses to microbial infections.

• 出版日期2012-7-30