Fcγ receptor dependent clearance is enhanced following lipopolysaccharide in vivo treatment

Lipopolysaccharides (LPS) occupy centre stage in the pathogenesis of gram-negative sepsis. Although LPS are potent stimulators of the mononuclear phagocyte system (MPS), their effects on immune complex (IC)-specific clearance have not yet been reported. In order to evaluate this issue, we examined the MPS function after LPS treatment by measuring intravascular removal rate of syngeneic erythocytes sensitized with specific immunoglobulin G (IgG) (EA). Our findings showed that LPS, directly or through the release of endogenous cytokines, enhance Fc gamma receptor (Fc gamma R)-dependent clearance. The EA uptake by liver, spleen and bone marrow was significantly increased leading to an effective clearance of immune complexes. Splenic antibody-dependent cellular cytotoxicity (ADCC), an in vitro indicator of Fc gamma R functionality, was also increased after in vivo LPS treatment. However, cytometric studies showed that endotoxin did not modify Fc gamma R expression on splenocytes, but markedly enhanced the expression of CD11b/CD18 (Mac-1), an adhesion molecule closely related to Fc gamma R activity. We conclude that LPS enhance Fc gamma R-dependent effector functions and suggest that this effect is mediated through alterations in adhesion molecules.