Journal Article

Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax

Myung-Chul Chung, Shelley C. Jorgensen, Taissia G. Popova, Charles L. Bailey and Serguei G. Popov

in FEMS Immunology & Medical Microbiology

Published on behalf of Federation of Microbiological Societies

Volume 54, issue 3, pages 309-318
Published in print December 2008 | ISSN: 0928-8244
Published online November 2008 | e-ISSN: 1574-695X | DOI: https://dx.doi.org/10.1111/j.1574-695X.2008.00480.x
Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax

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Abstract

Bacillus anthracis infection is associated with severe hemostatic disturbances but their roles and contribution to fatality remain incompletely characterized. We undertook analyses of circulating antithrombin levels during the course of infection using a comparison of lethal and nonlethal murine anthrax models. Plasma samples were obtained from DBA/2 mice challenged intraperitoneally with the spores of either toxigenic B. anthracis Sterne strain or nontoxigenic, avirulent delta Sterne strain. We found that plasma antithrombin levels were rapidly depleted in Sterne spore-challenged mice, concomitant with elevation of neutrophil elastase (NE) and massive syndecan shedding from the liver into circulation. The shed syndecan bound with antithrombin accelerated NE-mediated antithrombin proteolysis. The liver response to infection demonstrated strain-specific compensatory increases of antithrombin and syndecan gene transcription. Both bacterial strains induced changes in blood coagulation parameters consistent with the onset of disseminated intravascular coagulation. We propose that antithrombin depletion proceeding through activation of neutrophils and massive shedding of heparin-like syndecan from the liver into circulation contribute to anthrax coagulopathy.

Keywords: anthrax; disseminated intravascular coagulation; sepsis; antithrombin; syndecan

Journal Article.  6304 words.  Illustrated.

Subjects: Medical Microbiology and Virology ; Biotechnology ; Genetics and Genomics ; Microbiology ; Molecular and Cell Biology

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