Lipopolysaccharide-induced suppression of erythrocyte binding and phagocytosis via Fc gamma RI, Fc gamma RII, Fc gamma RIII, and CR3 receptors in murine macrophages.
In this study we have investigated the ability of lipopolysaccharide (LPS) to suppress binding and phagocytosis of erythrocytes via various receptors on mouse macrophages. Thioglycollate-elicited peritoneal macrophages were treated in vitro with LPS and the ability to bind and phagocytose radiolabeled sheep red blood cells was determined. We show that LPS can directly suppress phagocytosis of immunoglobulin G-opsonized and nonopsonized sheep red blood cells (SRBCs) by inflammatory macrophages. Suppression was dose dependent and was observed after 4 h of exposure. This effect lasted for at least 24 h following the removal of LPS. LPS suppressed the binding, rate, and absolute level of phagocytosis via Fc receptors. Phagocytosis via all Fc receptors (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) was suppressed by LPS. Furthermore, suppression was not limited to Fc receptor-mediated phagocytosis because binding and uptake of C3bi-opsonized SRBCs to CR3 receptors was also decreased following LPS treatment. LPS did not exert its effects via the production of interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, or interferon alpha/beta, because antibodies to these cytokines did not abrogate the effect. The ability of LPS to suppress binding and phagocytosis of microorganisms may contribute to the toxic effects of LPS during gram-negative sepsis by preventing or delaying elimination of bacteria by host macrophages.
Sundaram
R
R
Department of Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia.
O'Connor
M
M
Cicero
M
M
Ghaffar
A
A
Gangemi
J D
JD
Mayer
E P
EP
D000818:Animals; D003176:Complement C3 / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology; D003864:Depression, Chemical; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D011951:Receptors, Complement / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017452:Receptors, IgG / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012756:Sheep
D003176:Complement C3; D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011951:Receptors, Complement; D017452:Receptors, IgG; D003179:Complement C3b