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Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice

Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor... Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI −/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI −/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI −/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI +/+ macrophages. SLPI also affects B cell function. SLPI −/− B cells show more proliferation and IgM production after LPS treatment than SLPI +/+ B cells. Our results suggest that SLPI attenuates excessive inflammatory responses and thus assures balanced functioning of innate immunity. endotoxin shock innate immunity LPS NF-κB SLPI Footnotes ↵ * Abbreviations used in this paper: CLP, cecal ligation and puncture; ES, embryonic stem; HMG, high-mobility group; SLPI, secretory leukoprotease inhibitor; TLR, Toll-like receptor. Submitted: 17 October 2002 Accepted: 31 January 2003 Revision received 15 January 2003 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice

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References (24)

Publisher
Rockefeller University Press
Copyright
© 2003 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20021824
Publisher site
See Article on Publisher Site

Abstract

Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI −/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI −/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI −/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI +/+ macrophages. SLPI also affects B cell function. SLPI −/− B cells show more proliferation and IgM production after LPS treatment than SLPI +/+ B cells. Our results suggest that SLPI attenuates excessive inflammatory responses and thus assures balanced functioning of innate immunity. endotoxin shock innate immunity LPS NF-κB SLPI Footnotes ↵ * Abbreviations used in this paper: CLP, cecal ligation and puncture; ES, embryonic stem; HMG, high-mobility group; SLPI, secretory leukoprotease inhibitor; TLR, Toll-like receptor. Submitted: 17 October 2002 Accepted: 31 January 2003 Revision received 15 January 2003

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: Mar 3, 2003

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