Phorbol esters cause sequential activation and deactivation of complement receptors on polymorphonuclear leukocytes.
Phorbol myristate acetate (PMA) exerts a biphasic effect on receptors for C3b and C3bi of human polymorphonuclear leukocytes (PMN). The addition of PMA for 10 min enhances the capacity of these receptors to promote binding and phagocytosis of C3b- and C3bi-coated erythrocytes. Upon additional incubation for 60 min, the capacity of these receptors to bind and ingest ligand-coated erythrocytes decreases to levels below those of resting cells. Although PMA does cause increased expression of cell surface C3b and C3bi receptors, the sequential rise and fall of receptor activity cannot be accounted for by alterations in the number of surface receptors. It appears, rather, that PMA causes qualitative changes in these receptors, first an increase in receptor activity (activation) and then a decrease in receptor activity (deactivation). In contrast with its effects on C3 receptors, PMA causes only a reduction in the capacity of Fc receptors to bind and ingest IgG-coated erythrocytes. Deactivation of Fc receptors also appears to involve a qualitative alteration in receptors, because the binding affinity of soluble immune complexes is sharply reduced upon stimulation of PMN with PMA. To explore the role of phosphorylation in the sequential activation and deactivation of phagocytosis-promoting receptors, we loaded PMN with thiophosphate (thioP). This compound is incorporated into cellular nucleotides and proteins, and the resultant (thio)phosphorylated proteins are resistant to phosphatases. thioP-loaded cells show enhanced receptor activity, suggesting that activation of receptors is mediated by a phosphorylation event. Cells loaded with thioP and treated with PMA for 70 min do not deactivate C3 or Fc receptors, suggesting that the deactivation is the result of a dephosphorylation event.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects*; D006801:Humans; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D011951:Receptors, Complement / Q000032:analysis / Q000187:drug effects* / Q000276:immunology; D017463:Receptors, Complement 3b; D011961:Receptors, Fc / Q000187:drug effects; D017452:Receptors, IgG; D012397:Rosette Formation; D012756:Sheep / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D010704:Phorbols; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D017452:Receptors, IgG; D013755:Tetradecanoylphorbol Acetate