| Pivotal role for alpha1-antichymotrypsin in skin repair. | |
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MedLine Citation:
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PMID: 21693707 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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α1-Antichymotrypsin (α1-ACT) is a specific inhibitor of leukocyte-derived chymotrypsin-like proteases with largely unknown functions in tissue repair. By examining human and murine skin wounds, we showed that following mechanical injury the physiological repair response is associated with an acute phase response of α1-ACT and the mouse homologue Spi-2, respectively. In both species, attenuated α1-ACT/Spi-2 activity and gene expression at the local wound site was associated with severe wound healing defects. Topical application of recombinant α1-ACT to wounds of diabetic mice rescued the impaired healing phenotype. LC-MS analysis of α1-ACT cleavage fragments identified a novel cleavage site within the reactive center loop and showed that neutrophil elastase was the predominant protease involved in unusual α1-ACT cleavage and inactivation in nonhealing human wounds. These results reveal critical functions for locally acting α1-ACT in the acute phase response following skin injury, provide mechanistic insight into its function during the repair response, and raise novel perspectives for its potential therapeutic value in inflammation-mediated tissue damage. |
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Authors:
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Daniel C Hoffmann; Christine Textoris; Felix Oehme; Tobias Klaassen; Andreas Goppelt; Axel Römer; Burkhard Fugmann; Jeffrey M Davidson; Sabine Werner; Thomas Krieg; Sabine A Eming |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-06-21 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-15 Completed Date: 2011-10-19 Revised Date: 2011-10-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 28889-901 Citation Subset: IM |
Affiliation:
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Department of Dermatology, University of Cologne, 50931 Cologne, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Humans Leukocyte Elastase / genetics, metabolism Mice Peptides / genetics, metabolism* Serpins / genetics, metabolism* Skin / injuries, metabolism* Wound Healing / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Peptides; 0/SERPINA3 protein, human; 0/Serpins; 129712-63-6/lambda Spi-2; EC 3.4.21.37/Leukocyte Elastase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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