IAI Accepts, published online ahead of print on 9 November 2009

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Infect. Immun. doi:10.1128/IAI.00949-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CD44 DEFICIENCY IS ASSOCIATED WITH ENHANCED ESCHERICHIA COLI INDUCED PROINFLAMMATORY CYTOKINE AND CHEMOKINE RELEASE BY PERITONEAL MACROPHAGES

Gerritje J. W. van der Windt^*, Cornelis van 't Veer, Sandrine Florquin, and Tom van der Poll

Center of Infection and Immunity Amsterdam (CINIMA), Center for Experimental and Molecular Medicine (CEMM), and Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. Email: g.j.vanderwindt{at}amc.uva.nl.

CD44 is involved in several immune responses such as cellular adhesion, migration, proliferation and activation. Peritonitis is an important cause of sepsis and Escherichia (E.) coli is one of the major pathogens involved herein. We here sought to determine the role of CD44 in the host response to E. coli induced abdominal sepsis and to assess the function of CD44 in the activation of primary peritoneal macrophages by E. coli or LPS purified from this bacterium, using WT and CD44 knockout (KO) mice. CD44 KO mice demonstrated enhanced CXC chemokines levels in peritoneal lavage fluid already at 6 hours after infection, whereas tumor necrosis factor (TNF)- and interleukin (IL)-6 levels were elevated at 20 hours post infection. In line, CD44 KO peritoneal macrophages released more TNF- and macrophage inflammatory protein (MIP)-2 than WT cells upon stimulation with E. coli or E. coli LPS in the presence of autologous serum. In contrast, plasma TNF- levels were lower in CD44 KO mice, and CD44 KO blood leukocytes secreted similar amounts of TNF- and MIP-2 upon ex vivo incubation with E. coli or LPS. The proinflammatory phenotype of CD44 KO macrophages was not associated with an altered expression of inhibitors of Toll-like receptor signaling, whereas it could be partially reversed by addition of WT serum. CD44 deficiency did not impact on leukocyte recruitment into the peritoneal cavity or organ failure. These data suggest that CD44 differentially influences cytokine and chemokine release by different leukocyte subsets.