| First Author | Verjan Garcia N | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 5 | Pages | 2268-77 |
| PubMed ID | 21775684 | Mgi Jnum | J:179151 |
| Mgi Id | MGI:5301208 | Doi | 10.4049/jimmunol.1101008 |
| Citation | Verjan Garcia N, et al. (2011) SIRPalpha/CD172a regulates eosinophil homeostasis. J Immunol 187(5):2268-77 |
| abstractText | 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 alpha (SIRPalpha)/CD172a and a low, but significant, level of a tetraspanin CD63, whose upregulation is closely associated with degranulation. Cross-linking SIRPalpha/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 SIRPalpha/CD172a that lacks most of its cytoplasmic domain (SIRPalpha Cyto(-/-)). The SIRPalpha Cyto(-/-) eosinophils showed reduced viability, increased CD63 expression, and increased eosinophil peroxidase release with or without A23187 stimulation in vitro. In addition, SIRPalpha 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 SIRPalpha/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 SIRPalpha Cyto(-/-) mice compared with wild-type mice. Collectively, our results indicated that SIRPalpha/CD172a regulates eosinophil homeostasis, probably by interacting with CD47, with substantial effects on eosinophil survival. Thus, SIRPalpha/CD172a is a potential therapeutic target for eosinophil-associated diseases. |
