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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3033-3043. Prepublished online as a Blood First Edition Paper on July 28, 2009; DOI 10.1182/blood-2009-02-204966. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-02-204966v1 114/14/3033    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Hayashida, K. Articles by Park, P. W. PubMed PubMed Citation Articles by Hayashida, K. Articles by Park, P. W. Related Collections Immunobiology Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Syndecan-1 shedding facilitates the resolution of neutrophilic inflammation by removing sequestered CXC chemokines Kazutaka Hayashida1, William C. Parks2, and Pyong Woo Park1 1 Division of Respiratory Diseases, Children's Hospital, Harvard Medical School, Boston, MA; and 2 Center for Lung Biology, University of Washington, Seattle Heparan sulfate binds to and regulates many inflammatory mediators in vitro, suggesting that it serves an important role in directing the progression and outcome of inflammatory responses in vivo. Here, we evaluated the role of syndecan-1, a major heparan sulfate proteoglycan, in modulating multiorgan host injury responses in murine endotoxemia. The extent of systemic inflammation was similar between endotoxemic syndecan-1–null and wild-type mice. However, high levels of CXC chemokines (KC and MIP-2), particularly at later times after LPS, were specifically sustained in multiple organs in syndecan-1–null mice and associated with exaggerated neutrophilic inflammation, organ damage, and lethality. Syndecan-1 shedding was activated in several organs of endotoxemic wild-type mice, and this associated closely with the removal of tissue-bound CXC chemokines and resolution of accumulated neutrophils. Moreover, administration of a shedding inhibitor exacerbated disease by impeding the removal of CXC chemokines and neutrophils, whereas administration of heparan sulfate inhibited the accumulation of CXC chemokines and neutrophils in tissues and attenuated multiorgan injury and lethality. These data show that syndecan-1 shedding is a critical endogenous mechanism that facilitates the resolution of neutrophilic inflammation by aiding the clearance of proinflammatory chemokines in a heparan sulfate–dependent manner. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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