Expression of MHC class II molecules contributes to lipopolysaccharide responsiveness

Activation of phagocytes by lipopolysaccharide (LPS) causes synthesis and s ecretion of various mediators of inflammation. CD14, a glycosylphosphatidyl inositol-anchored monocytic antigen serving as receptor for LPS, and member s of the family of Toll-like receptors mediate cellular activation in respo nse to LPS. Here we investigated whether expression of MHC class II molecul es modified the response to LPS. Comparing LPS responsiveness of human and murine cells differing for expression of MHC class II molecules, we found t hat lack or a low level of expression of MHC class II molecules resulted in diminished secretion of proinflammatory cytokines following stimulation wi th LPS. Thus, expression of MHC class II molecules modifies LPS responsiven ess, a finding suggesting that these molecules contribute to the pathogenes is not only of exotoxin-triggered toxic shock but also of endotoxin-trigger ed septic shock. Additionally to their role in antigen-specific immunity MH C class II molecules may influence the inflammatory response triggered by m icrobial constituents.