View : 31 Download: 0

SIRPα/CD172α regulates eosinophil homeostasis

Title
SIRPα/CD172α regulates eosinophil homeostasis
Authors
Garcia N.V.Umemoto E.Saito Y.Yamasaki M.Hata E.Matozaki T.Murakami M.Jung Y.-J.Woo S.-Y.Seoh J.-Y.Jang M.H.Aozasa K.Miyasaka M.
Ewha Authors
서주영우소연
SCOPUS Author ID
서주영scopus; 우소연scopus
Issue Date
2011
Journal Title
Journal of Immunology
ISSN
0022-1767JCR Link
Citation
vol. 187, no. 5, pp. 2268 - 2277
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Eosinophils are abundant in the lamina propria of the small intestine, but they rarely show degranulation in situ under steady-state conditions. In this study, using two novel mAbs, we found that intestinal eosinophils constitutively expressed a high level of an inhibitory receptor signal regulatory protein α (SIRPα)/CD172a and a low, but significant, level of a tetraspanin CD63, whose upregulation is closely associated with degranulation. Cross-linking SIRPα/CD172a on the surface of wild-type eosinophils significantly inhibited the release of eosinophil peroxidase induced by the calcium ionophore A23187, whereas this cross-linking effect was not observed in eosinophils isolated from mice expressing a mutated SIRPα/CD172a that lacks most of its cytoplasmic domain (SIRPα Cyto -/-). The SIRPα Cyto -/- eosinophils showed reduced viability, increased CD63 expression, and increased eosinophil peroxidase release with or without A23187 stimulation in vitro. In addition, SIRPα Cyto -/- mice showed increased frequencies of Annexin V-binding eosinophils and free MBP +CD63 + extracellular granules, as well as increased tissue remodeling in the small intestine under steady-state conditions. Mice deficient in CD47, which is a ligand for SIRPα/CD172a, recapitulated these phenomena. Moreover, during Th2-biased inflammation, increased eosinophil cell death and degranulation were obvious in a number of tissues, including the small intestine, in the SIRPa Cyto -/- mice compared with wild-type mice. Collectively, our results indicated that SIRPα/CD172a regulates eosinophil homeostasis, probably by interacting with CD47, with substantial effects on eosinophil survival. Thus, SIRPα/CD172a is a potential therapeutic target for eosinophil-associated diseases. Copyright © 2011 by The American Association of Immunologists, Inc.
DOI
10.4049/jimmunol.1101008
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE