Cutting Edge: An Endogenous Pathway to Systemic Inflammatory Response Syndrome (SIRS)-Like Reactions through Toll-Like Receptor 4

Geoffrey B. Johnson, Gregory J. Brunn, Jeffrey L. Platt

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

Systemic inflammatory response syndrome (SIRS) is typically associated with trauma, surgery, or acute pancreatitis. SIRS resembles sepsis, triggered by exogenous macromolecules such as LPS acting on Toll-like receptors. What triggers SIRS in the absence of infection, however, is unknown. In this study, we report that a SIRS-like response can be induced in mice by administration of soluble heparan sulfate, a glycosaminoglycan associated with nucleated cells and extracellular matrices, and by elastase, which cleaves and releases heparan sulfate proteoglycans. The ability of heparan sulfate and elastase to induce SIRS depends on functional Toll-like receptor 4, because mutant mice lacking that receptor or its function do not respond. These results provide a molecular explanation for the initiation of SIRS.

Original languageEnglish (US)
Pages (from-to)20-24
Number of pages5
JournalJournal of Immunology
Volume172
Issue number1
DOIs
StatePublished - Jan 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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