Lipopolysaccharide enhances FcgammaR-dependent functions in vivo through CD11b/CD18 up-regulation.
Fc receptors for immunoglobulin G (IgG) (FcgammaR) mediate several defence mechanisms in the course of inflammatory and infectious diseases. In Gram-negative infections, cellular wall lipopolysaccharides (LPS) modulate different immune responses. We have recently demonstrated that murine LPS in vivo treatment significantly increases FcgammaR-dependent clearance of immune complexes (IC). In addition, we and others have reported the induction of adhesion molecules on macrophages and neutrophils by LPS in vivo and by tumour necrosis factor-alpha (TNF-alpha) in vitro. The aim of this paper was to investigate CD11b/CD18 participation in LPS enhancing effects on Fcgamma-dependent functionality of tissue macrophages. Our results have demonstrated that LPS can enhance antibody-dependent cellular cytotoxicity (ADCC) and IC-triggered cytotoxicity (IC-Ctx), two reactions which involve the Fcgamma-receptor but different lytic mechanisms. In vitro incubation of splenocytes from LPS-treated mice with anti-CD11b/CD18 abrogated ADCC and IC-Ctx enhancement, without affecting FcgammaR expression. Similar results were obtained with physiological concentrations of fibrinogen. In this way cytotoxic values of LPS-splenocytes decreased to the basal levels of control mice. Time and temperature requirements for such inhibition strongly suggested that anti-CD11b/CD18 could modulate intracellular signals leading to downregulation of FcgammaR functionality. Data presented herein support the hypothesis that functional and/or physical associations between integrins and FcgammaR could be critical for the modulation of effector functions during an inflammatory response.
Rubel
C
C
División Inmunología, Academia Nacional de Medicina, Buenos Aires, Argentina.
Miliani De Marval
P
P
Vermeulen
M
M
Isturiz
M A
MA
Palermo
M S
MS
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology*; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005340:Fibrinogen / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017452:Receptors, IgG / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D018821:CD18 Antigens; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; D005340:Fibrinogen; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate