IgG-coated erythrocytes augment the lipopolysaccharidestimulated increase in serum tumor necrosis factor-α
Previous studies have shown that the injection of IgG-coated erythrocytes (EIgG) caused an increase in the mortality rate due to bacterial lipopolysaccharide (LPS). This observation led to the present evaluation of the effect of EIgG on the LPS-stimulated increase in serum tumor necrosis factor-α (TNF-α) levels and TNF-α secretion by macrophages. The prior injection of EIgG augmented the increase in LPS-stimulated serum TNF-α levels ninefold at 1 h after LPS. Serum TNF-α levels were augmented when LPS was injected 2 or 6 h after EIgG but not at 0.5 or 12 h after EIgG. Complement activation caused by EIgG may contribute to the priming for TNF-α, because activation of complement with cobra venom factor caused a threefold augmentation of the LPS-stimulated serum TNF-α levels. Isolated macrophages that had ingested EIgG or were adherent to immobilized IgG showed augmented TNF-α secretion in response to LPS. Thus clearance of immune complexes from the blood can augment the LPS-stimulated increase in serum TNF-α levels that is due, in part, to complement activation and signaling via FcγR.