Fcgamma-receptor signaling augments the LPS-stimulated increase in serum tumor necrosis factor-alpha levels.
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 Fcgamma-receptor (FcgammaR) signaling and complement activation in the effect of EIgG on the TNF-alpha response to LPS. The role of FcgammaR was determined using FcR gamma-chain knockout mice that lack functional FcgammaRI and FcgammaRIII. 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 FcgammaR-deficient animals. Heat-damaged erythrocytes also augmented the TNF-alpha response to LPS. This effect was absent in FcgammaR-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 FcgammaR signaling primarily mediates the augmented serum TNF-alpha response to LPS caused by EIgG.
Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208, USA.
M L
ML
Refici
D W
DW
Metzger
B P
BP
Arulanandam
M R
MR
Lennartz
D J
DJ
Loegering
D000818:Animals; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology; D004546:Elapid Venoms / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004546:Elapid Venoms; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor