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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/G481    most recent 00299.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Zanardo, R. C. O. Articles by Wallace, J. L. Search for Related Content PubMed PubMed Citation Articles by Zanardo, R. C. O. Articles by Wallace, J. L.

INFLAMMATION/IMMUNITY/MEDIATORS

Annexin-1 is an endogenous gastroprotective factor against indomethacin-induced damage

¹Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, Canada; and ²The William Harvey Research Institute, Queen Mary School of Medicine & Dentistry, University of London, London, England

Submitted 8 July 2004 ; accepted in final form 28 September 2004

Adherence of neutrophils to the vascular endothelium is an early and critical event in the pathogenesis of gastric injury induced by NSAIDs. Pretreatment with glucocorticoids has been shown to prevent NSAID-induced neutrophil adherence and, in turn, to protect the stomach from injury. Some of the anti-inflammatory effects of glucocorticoids, including inhibition of neutrophil adherence, are mediated via the release of annexin-1. In this study, we assessed the contribution of annexin-1 to the protective actions of a glucocorticoid (dexamethasone) against indomethacin-induced gastric damage. Dexamethasone pretreatment markedly reduced the extent of indomethacin-induced gastric damage in rats. Immunoneutralization of annexin-1 resulted in a reversal of the gastroprotective actions of dexamethasone. Similarly, pretreatment with either of two antagonists of the formyl peptide receptor family, to which annexin-1 binds, reversed the gastroprotective effects of dexamethasone. The inhibitory effects of dexamethasone on indomethacin-induced leukocyte adherence in the mesenteric microcirculation were abolished by pretreatment with an antibody directed against annexin-1 or with an antagonist of the formyl peptide receptors. These results demonstrate that annexin-1 mediates the gastroprotective effects of a glucocorticoid against NSAID-induced damage. We propose that in some circumstances, annexin-1 plays an important role as an endogenous mediator of mucosal defense.

nonsteroidal anti-inflammatory; stomach; ulcer; glucocorticoid

This article has been cited by other articles:

				J. L. Wallace Prostaglandins, NSAIDs, and Gastric Mucosal Protection: Why Doesn't the Stomach Digest Itself? Physiol Rev, October 1, 2008; 88(4): 1547 - 1565. [Abstract] [Full Text] [PDF]

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