Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-8-22
pubmed: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 ? (SIRP?)/CD172a and a low, but significant, level of a tetraspanin CD63, whose upregulation is closely associated with degranulation. Cross-linking SIRP?/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 SIRP?/CD172a that lacks most of its cytoplasmic domain (SIRP? Cyto(-/-)). The SIRP? Cyto(-/-) eosinophils showed reduced viability, increased CD63 expression, and increased eosinophil peroxidase release with or without A23187 stimulation in vitro. In addition, SIRP? 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 SIRP?/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 SIRP? Cyto(-/-) mice compared with wild-type mice. Collectively, our results indicated that SIRP?/CD172a regulates eosinophil homeostasis, probably by interacting with CD47, with substantial effects on eosinophil survival. Thus, SIRP?/CD172a is a potential therapeutic target for eosinophil-associated diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2268-77
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21775684-Animals, pubmed-meshheading:21775684-Antigens, CD, pubmed-meshheading:21775684-Antigens, CD47, pubmed-meshheading:21775684-Antigens, CD63, pubmed-meshheading:21775684-Blotting, Western, pubmed-meshheading:21775684-Cell Degranulation, pubmed-meshheading:21775684-Cell Separation, pubmed-meshheading:21775684-Chromatography, Liquid, pubmed-meshheading:21775684-Eosinophils, pubmed-meshheading:21775684-Female, pubmed-meshheading:21775684-Flow Cytometry, pubmed-meshheading:21775684-Fluorescent Antibody Technique, pubmed-meshheading:21775684-Homeostasis, pubmed-meshheading:21775684-Immunity, Mucosal, pubmed-meshheading:21775684-Immunoprecipitation, pubmed-meshheading:21775684-Intestinal Mucosa, pubmed-meshheading:21775684-Mass Spectrometry, pubmed-meshheading:21775684-Mice, pubmed-meshheading:21775684-Mice, Inbred BALB C, pubmed-meshheading:21775684-Mice, Inbred C57BL, pubmed-meshheading:21775684-Platelet Membrane Glycoproteins, pubmed-meshheading:21775684-Receptors, Immunologic
pubmed:year
2011
pubmed:articleTitle
SIRP?/CD172a regulates eosinophil homeostasis.
pubmed:affiliation
Laboratory of Immunodynamics, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't