title: Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor.
abstract: When a cell undergoes apoptosis, phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. PS acts as an "eat-me" 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.
authors: Department of Immunology, Division of Biomedical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Chigusa
authors: C
authors: Nakahashi-Oda
authors: Satoko
authors: S
authors: Tahara-Hanaoka
authors: Masamichi
authors: M
authors: Shoji
authors: Yasushi
authors: Y
authors: Okoshi
authors: Takako
authors: T
authors: Nakano-Yokomizo
authors: Nobuhiro
authors: N
authors: Ohkohchi
authors: Teruhito
authors: T
authors: Yasui
authors: Hitoshi
authors: H
authors: Kikutani
authors: Shin-ichiro
authors: S
authors: Honda
authors: Kazuko
authors: K
authors: Shibuya
authors: Shigekazu
authors: S
authors: Nagata
authors: Akira
authors: A
authors: Shibuya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; C476771:LMIR1 protein, mouse; D010718:Phosphatidylserines; D011971:Receptors, Immunologic