| Vitronectin Inhibits Neutrophil Apoptosis Through Activation of Integrin Associated Signaling Pathways. | |
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MedLine Citation:
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PMID: 22281987 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Vitronectin is present in large concentrations in serum and the extracellular matrix. While vitronectin is known to modulate neutrophil adhesion and chemotaxis, and to contribute to neutrophil associated proinflammatory processes, a role in apoptosis has not been demonstrated. In the present studies, we found that neutrophils demonstrated more rapid progression to spontaneous or TRAIL induced apoptosis when incubated under vitronectin free conditions than when vitronectin was present. The ability of native vitronectin to delay neutrophil apoptosis was not recapitulated by the vitronectin somatomedin B (SMB) domain. In contrast, inclusion of the RGDfv peptide in cultures containing vitronectin resulted in enhanced neutrophil apoptosis, showing that the vitronectin RGD domain was responsible for the anti-apoptotic effects of vitronectin. Addition of antibodies to β(1), β(3), or β(5), but not to β(2) or β(4) integrins, reversed the ability of vitronectin to diminish neutrophil apoptosis. The ability of vitronectin to enhance neutrophil viability was dependent on activation of PI3-K and Erk1/2 kinases, but not on the p38 kinase. Increased numbers of apoptotic neutrophils were present in the lungs of LPS treated transgenic vitronectin deficient (vtn(-/-)) mice, as compared to control vtn(+/+) mice. These results demonstrate a novel anti-apoptotic function for vitronectin. |
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Authors:
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Hong-Beom Bae; Jaroslaw W Zmijewski; Jessy S Deshane; Degui Zhi; Lawrence C Thompson; Cynthia B Peterson; David D Chaplin; Edward Abraham |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-26 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: - ISSN: 1535-4989 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Medicine, University of Alabama at Birmingham, Birmingham, AlabaUnited States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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