RRC ID |
18088
|
著者 |
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.
|
タイトル |
Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor.
|
ジャーナル |
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.
|
巻・号 |
209(8)
|
ページ |
1493-503
|
公開日 |
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 |
11.743
|
引用数 |
51
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
IMMUNOLOGY
|
リソース情報 |
実験動物マウス |
RBRC01888 |