CD44 as a novel target for treatment of staphylococcal enterotoxin B-induced acute inflammatory lung injury.

Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In the current study, we investigated the role of CD44 in ALI/ARDS. Intranasal exposure of CD44 wild-type mice to SEB led to a significant increase in the expression of CD44 on lung mononuclear cells. CD44 knockout mice developed significantly reduced SEB-induced ALI/ARDS, through reduced inflammatory cytokine production and reduced lung inflammatory cells, compared to similarly treated CD44 wild-type mice. Mechanistically, deletion of CD44 altered SEB-induced cytokine production in the lungs and reduced the ability of SEB-exposed leukocytes to bind to lung epithelial cells. Finally, treatment of SEB-exposed mice with anti-CD44 mAbs led to significant reduction in vascular permeability, reduction in cytokine production, and prevented inflammatory cell infiltration in the lungs. Together, these results suggest the possibility of targeting CD44 for the treatment of SEB-induced ALI/ARDS.