Fc γ ‐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 tritiumlabelled cation tetraphenylphosphonium, [ 3 H]Ph 4 P + . 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 E 2 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 E 2 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 E 2 synthesis comparable to that mediated by either aggregated human IgGs or Fc fragments. Our previous results on Fc γ ‐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 γ receptors on human fibroblasts is the stimulus for plasma membrane depolarization leading to an enhanced prostaglandin E 2 release.