CD44 Deficiency Is Associated with EnhancedEscherichia coli-Induced Proinflammatory Cytokine and Chemokine Release by Peritoneal Macrophages
- 1 January 2010
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (1), 115-124
- https://doi.org/10.1128/iai.00949-09
Abstract
CD44 is involved in several immune responses, such as cellular adhesion, migration, proliferation, and activation. Peritonitis is an important cause of sepsis, andEscherichia coliis one of the major pathogens involved therein. We sought to determine the role of CD44 in the host response toE. coli-induced abdominal sepsis and to assess the function of CD44 in the activation of primary peritoneal macrophages byE. colior lipopolysaccharide (LPS) purified from this bacterium by using wild-type (WT) and CD44 knockout (KO) mice. CD44 KO mice already demonstrated enhanced CXC chemokine levels in peritoneal lavage fluid at 6 h after infection, whereas tumor necrosis factor alpha (TNF-α) and interleukin-6 levels were elevated at 20 h postinfection. In line with this, CD44 KO mouse peritoneal macrophages released more TNF-α and macrophage inflammatory protein 2 (MIP-2) than did WT cells upon stimulation withE. colior LPS in the presence of autologous serum. In contrast, plasma TNF-α levels were lower in CD44 KO mice and CD44 KO blood leukocytes secreted similar amounts of TNF-α and MIP-2 uponex vivoincubation withE. colior 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.Keywords
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