| Metalloproteinase-mediated shedding of integrin β2 promotes macrophage efflux from inflammatory sites. | |
| | |
MedLine Citation:
|
PMID: 22170060 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Macrophage exiting from inflammatory sites is critical to limit the local innate immune response. With tissue insult, resident tissue macrophages rapidly efflux to lymph nodes where they modulate the adaptive immune response, and inflammatory macrophages attracted to the site of injury then exit during the resolution phase. However, the mechanisms that regulate macrophage efflux are poorly understood. This study has investigated soluble forms of integrin β2 whose levels are elevated in experimental peritonitis at times when macrophages are exiting the peritoneum, suggesting that its proteolytic shedding may be involved in macrophage efflux. Both constitutive and inducible metalloproteinase-dependent shedding of integrin β2 from mouse macrophages is demonstrated. Soluble integrin β2 is primarily released as a heterodimeric complex with αM that retains its ability to bind its ligands intracellular adhesion molecule-1, fibrin, and collagen and thus may serve as a soluble antagonist. In a model of accelerated exiting, administration of a metalloproteinase inhibitor prevents macrophage efflux by 50% and impedes loss of macrophage integrin β2 from the cell surface. Exiting of peritoneal macrophages in mice lacking integrin β2 is accelerated, and antibody disruption of integrin β2-substrate interactions can reverse 50% of the metalloprotease inhibitor blockade of macrophage exiting. Thus, our study demonstrates the ability of metalloproteinase-mediated shedding of integrin β2 to promote macrophage efflux from inflammatory sites, and the release of soluble integrin heterodimers may also limit local inflammation. |
| | |
Authors:
|
Ivan G Gomez; Jingjing Tang; Carole L Wilson; Wei Yan; Jay W Heinecke; John M Harlan; Elaine W Raines |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-14 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Washington, United States; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Structural Characterization of a Viral Ortholog of the human DNA glycosylase NEIL1 Bound to Thymine ...
Next Document: Two independent mechanisms promote expression of an N-terminal truncated USP18 isoform with higher d...