Lipopolysaccharide enhances Fc gamma R-dependent functions in vivo throughCD11b/CD18 up-regulation

Fc receptors for immunoglobulin G (IgG) (Fc gamma R) mediate several defenc e mechanisms in the course of inflammatory and infectious diseases. In Gram -negative infections, cellular wall lipopolysaccharides (LPS) modulate diff erent immune responses. We have recently demonstrated that murine LPS in vi vo treatment significantly increases Fc gamma R-dependent clearance of immu ne complexes (IC). In addition, we and others have reported the induction o f adhesion molecules on macrophages and neutrophils by LPS in vivo and by t umour necrosis factor-alpha (TNF-alpha) in vitro. The aim of this paper was to investigate CD11b/CD18 participation in LPS enhancing effects on Fc gam ma-dependent functionality of tissue macrophages. Our results have demonstr ated that LPS can enhance antibody-dependent cellular cytotoxicity (ADCC) a nd IC-triggered cytotoxicity (IC-Ctx), two reactions which involve the Fc g amma-receptor but different lytic mechanisms. In vitro incubation of spleno cytes from LPS-treated mice with anti-CD11b/CD18 abrogated ADCC and IC-Ctx enhancement, without affecting Fc gamma R expression. Similar results were obtained with physiological concentrations of fibrinogen. In this way cytot oxic values of LPS-splenocytes decreased to the basal levels of control mic e. Time and temperature requirements for such inhibition strongly suggested that anti-CD11b/CD18 could modulate intracellular signals leading to downr egulation of Fc gamma R functionality. Data presented herein support the hy pothesis that functional and/or physical associations between integrins and Fc gamma R could be critical for the modulation of effector functions duri ng an inflammatory response.