Search

Past investigations have indicated that the injection of IgC-coated erythrocytes (EIgC) causes a rise in the mortality rate because of bacterial lipopolysaccharide (LPS). The effect of EIgC on LPS-stimulated increase in secretion by macrophages was studied. Isolated macrophages that had ingested EIgC or were adherent to immobilized IgC indicated increased tumor necrosis factor-alpha levels that is partly caused by complement activation and signaling through FclambdaR.

The contribution of blood flow to the development of insulin resistance in denervated muscles was investigated in a number of muscles from the denervated limb of rats. Results indicate that blood flow to muscle is dependent on the type of muscle fiber and the duration of denervation. Changes in blood flow to denervated muscles is not a contributory factor in the development of insulin resistance.

Refici, Marion L., Dennis W. Metzger, Bernard P. Arulanandam, Michelle R. Lennartz, and Daniel J. Loegering. Fc[Gamma]-receptor signaling augments the LPS-stimulated increase in serum tumor necrosis factor-[Alpha] levels. Am J Physiol Regulatory Integrative Comp Physiol 280: R1037-R1044, 2001.--The phagocytosis of IgG-coated erythrocytes (EIgG) has been shown to augment the bacterial lipopolysaccharide (LPS)-stimulated increase in serum tumor necrosis factor-[Alpha] (TNF-[Alpha]) levels. The present study evaluated the role of Fc[Gamma]-receptor (Fc[Gamma]R) signaling and complement activation in the effect of EIgG on the TNF-[Alpha] response to LPS. The role of Fc[Gamma]R was determined using FcR [Gamma]-chain knockout mice that lack functional Fc[Gamma]RI and Fc[Gamma]RIII. In wild-type animals, EIgG caused a 16-fold augmentation of the serum TNF-[Alpha] response to LPS, whereas there was no augmentation in the Fc[Gamma]R-deficient animals. Heat-damaged erythrocytes also augmented the TNF-[Alpha] response to LPS. This effect was absent in Fc[Gamma]R-deficient animals. An IgG antibody against heated erythrocytes was detected in mouse serum. The complement activation caused by EIgG had little effect on the LPS-stimulated increase in serum TNF-[Alpha] levels as indicated by activation of complement with cobra venom factor or IgM-coated erythrocytes as well as studies with C5-deficient mice. These results indicate that Fc[Gamma]R signaling primarily mediates the augmented serum TNF-[Alpha] response to LPS caused by EIgG. Fc receptor [Gamma]-chain knockout mice; sepsis; heat-damaged erythrocytes; complement activation; C5 knockout mice; cobra venom factor