CD44 is involved in several immune responses, such as cellular adhesion, migration, proliferation, and activation.
Peritonitis is an important cause of
sepsis, and Escherichia coli is one of the major pathogens involved therein. We 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
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-alpha) and
interleukin-6 levels were elevated at 20 h postinfection. In line with this, CD44 KO mouse peritoneal macrophages released more
TNF-alpha and
macrophage inflammatory protein 2 (MIP-2) than did WT cells upon stimulation with E. coli or LPS in the presence of autologous serum. In contrast, plasma
TNF-alpha levels were lower in CD44 KO mice and CD44 KO blood leukocytes secreted similar amounts of
TNF-alpha 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.