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 complex es 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 produ ction. Similar results were obtained with IgG-containing immune comple xes and Con A. The presence of monomeric IgA or IgG did not increase T NF secretion. Both IgA and IgG immune complexes also increased monocyt e interleukin-1beta (IL-1beta) production. Galactose inhibited the eff ect of IgA but not IgG immune complexes, while mannose inhibited the e ffect of Con A. Prednisolone abrogated TNF production, while indometha cin enhanced TNF production in all instances where cross-linking of pl asma membrane receptors was achieved. These results indicate that acti vation of Fcalpha receptors (FcalphaR), FcgammaR or mannose receptors of the human monocyte plasma membrane by cross-linking results in incr eased TNF and IL-1beta secretion. These findings may be of particular relevance in the pathogenesis of IgA immune complex-mediated disease.