Journal of leukocyte biology
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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. ⋯ 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.
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Tumor necrosis factor alpha (TNF-alpha) has been shown to be an important mediator of the lethal effects of endotoxin in several experimental models of septic shock. However, studies with a recombinant human interleukin-1 (IL-1) receptor antagonist protein (IL-1ra) suggest a role for IL-1 as a mediator of septic shock as well. In the present study, we show that mice treated in vivo with Corynebacterium parvum are primed for the production of interferon-gamma (IFN-gamma) and exhibit an enhanced capacity to produce serum IL-1 alpha, TNF-alpha, and IL-6 when challenged intravenously with lipopolysaccharide (LPS). ⋯ These results indicate that TNF-alpha and IFN-gamma are major mediators of endotoxin shock in C. parvum-treated mice. The results further suggest that the IFN-gamma produced by C. parvum-primed mice in response to an LPS challenge serves as a stimulus for enhanced production of TNF-alpha and IL-1 alpha. These findings are consistent with an increasing body of evidence suggesting a major role for IFN-gamma in lethal endotoxemia.