Protein kinase C controls Fc gamma receptor-mediated endocytosis in human neutrophils.

The aim of this study is to clarify which signaling mechanism operates in Fc gamma receptor-mediated endocytosis in human neutrophils. Endocytosis of immune complexes was inhibited by antibodies directed to cell membrane phospholipase C (PLC) and A2 (PLA2) (maximal inhibition obtained was 57% and 28%, respectively), being almost abolished by these antibodies if used in combination (up to 91% inhibition). The protein kinase C (PKC) activator, phorbol 12,13-dibutyrate, reversed this inhibitory effect. Four different PKC inhibitors (H-7, palmitoylcarnitine, sphingosine, and tamoxifen) produced a dose-dependent inhibition of endocytosis, up to over 80% in each case. H-8 (1-10 microM) which inhibits cyclic nucleotide protein kinases but not PKC had no effect upon endocytosis. It is concluded that Fc gamma receptor-induced activation of PLC and PLA2 triggers endocytosis by activation of PKC.