Cross-linking of monocyte plasma membrane Fc alpha, Fc gamma or mannose receptors induces TNF production.

We have studied and compared the effects of IgA and IgG immune complexes and concanavalin A (Con A) on human monocyte tumour necrosis factor (TNF) production. The presence of IgA-containing immune complexes in monocyte monolayers resulted in a dose-dependent increase of TNF production. Similar results were obtained with IgG-containing immune complexes and Con A. The presence of monomeric IgA or IgG did not increase TNF secretion. Both IgA and IgG immune complexes also increased monocyte interleukin-1 beta (IL-1 beta) production. Galactose inhibited the effect of IgA but not IgG immune complexes, while mannose inhibited the effect of Con A. Prednisolone abrogated TNF production, while indomethacin enhanced TNF production in all instances where cross-linking of plasma membrane receptors was achieved. These results indicate that activation of Fc alpha receptors (Fc alpha R), Fc gamma R or mannose receptors of the human monocyte plasma membrane by cross-linking results in increased TNF and IL-1 beta secretion. These findings may be of particular relevance in the pathogenesis of IgA immune complex-mediated disease.