Fc gamma-receptor-mediated changes in the plasma membrane potential induce prostaglandin release from human fibroblasts.
Binding of aggregated human immunoglobulin G (IgG) on diploid human fibroblasts leads to a rapid depolarization of the cells within 1-2 min. We resolved this membrane potential change into its plasma membrane and mitochondrial membrane components by measuring the transmembrane distribution of the lipophilic tritium-labelled cation tetraphenylphosphonium, [3H]Ph4P+. The responsibility of the plasma membrane for the membrane potential change, induced by binding of IgGs, is demonstrated. The IgG-induced membrane depolarization leads to the induction of prostaglandin E2 synthesis. Aggregated immunoglobulins (IgG) are specifically bound via the Fc portion because only binding of Fc fragments, in contrast to (Fab')2 fragments, leads to a stimulation of prostaglandin E2 synthesis comparable to that mediated by IgGs. Depolarization of the plasma membrane by short incubation of the fibroblasts in high-K+ buffer (5 min) results in a stimulation of prostaglandin E2 synthesis comparable to that mediated by either aggregated human IgGs or Fc fragments. Our previous results on Fc gamma-receptor-mediated antigen-IgG-antibody complex internalization showed that a maximum uptake of these complexes could be detected 60-90 min after binding. Therefore, we conclude that not internalisation but binding of aggregated IgGs to the Fc gamma receptors on human fibroblasts is the stimulus for plasma membrane depolarization leading to an enhanced prostaglandin E2 release.
D000936:Antigen-Antibody Complex / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D015232:Dinoprostone; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D012964:Sodium / Q000378:metabolism; D014316:Tritium
D000936:Antigen-Antibody Complex; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D011453:Prostaglandins; D011458:Prostaglandins E; D011961:Receptors, Fc; D017452:Receptors, IgG; D014316:Tritium; D012964:Sodium; D015232:Dinoprostone; C013289:tetraphenylphosphonium