RRC ID 18088
Author Nakahashi-Oda C, Tahara-Hanaoka S, Shoji M, Okoshi Y, Nakano-Yokomizo T, Ohkohchi N, Yasui T, Kikutani H, Honda S, Shibuya K, Nagata S, Shibuya A.
Title Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor.
Journal J. Exp. Med.
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.
Volume 209(8)
Pages 1493-503
Published 2012-7-30
DOI 10.1084/jem.20120096
PII jem.20120096
PMID 22826299
PMC PMC3409498
MeSH Animals Apoptosis / immunology* Chemokines / immunology Chemokines / metabolism Cytokines / immunology Cytokines / metabolism Humans Inflammation / immunology* Inflammation / metabolism Inflammation / pathology Macrophages / immunology Macrophages / metabolism Mast Cells / immunology* Mast Cells / metabolism Mast Cells / pathology Mice Mice, Inbred BALB C Mice, Inbred C57BL NIH 3T3 Cells Neutrophil Infiltration / immunology Neutrophils / immunology Neutrophils / metabolism Phagocytosis / immunology Phosphatidylserines / immunology Phosphatidylserines / metabolism Receptors, Immunologic / immunology* Receptors, Immunologic / metabolism*
IF 10.79
Times Cited 32
Mice C57BL/6-Wsh/Wsh (RBRC01888)