Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor

J Exp Med. 2012 Jul 30;209(8):1493-503. doi: 10.1084/jem.20120096. Epub 2012 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Chemokines
  • Cytokines
  • LMIR1 protein, mouse
  • Phosphatidylserines
  • Receptors, Immunologic