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.
Moraru
I I
II
Division of Cell Biology, Faculty of Medicine, Bucharest, Romania.
Laky
M
M
Stãnescu
T
T
Buzilã
L
L
Popescu
L M
LM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000943:Antigens, Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D010172:Palmitoylcarnitine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D015398:Signal Transduction; D013110:Sphingosine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007546:Isoquinolines; D010879:Piperazines; D011961:Receptors, Fc; D017452:Receptors, IgG; D013629:Tamoxifen; D010172:Palmitoylcarnitine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013110:Sphingosine