Involvement of protein kinase Cdelta in the activation of NADPH oxidase and the phagocytosis of neutrophils.
This experiment was performed to clarify the role of protein kinase C (PKC) delta in NADPH oxidase-dependent O(2-) production and actin polymerization followed by phagocytosis in neutrophils. Bovine neutrophils and human neutrophil-like differentiated HL-60 (dHL-60) cells were stimulated with serum-opsonized zymosan (OZ) and fMet-Leu-Phe (fMLP), respectively. Rottlerin, a specific inhibitor of PKCdelta, attenuated the production of O(2-) from NADPH oxidase in both neutrophils and dHL-60 cells. However, it did not inhibit the translocation of p47(phox) from the cytosol to the membrane in either type of cell or the phosphorylation of p47(phox) in dHL-60 cells. GF109203X (GFX), an inhibitor of cPKC, attenuated not only the production of O(2-) but also the translocation of p47(phox) in both cells. Furthermore, rottlerin significantly attenuated the ingestion of opsonized particles and the formation of F-actin in OZ-stimulated neutrophils, whereas, GFX did not affect those phagocytic processes. These results suggest that both PKCdelta and cPKC regulate NADPH oxidase through different pathways, but only PKCdelta regulates the phagocytic function in neutrophils.
Waki
Kenji
K
Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060 0818, Japan.
Inanami
Osamu
O
Yamamori
Tohru
T
Nagahata
Hajime
H
Kuwabara
Mikinori
M
D000098:Acetophenones / Q000494:pharmacology; D000199:Actins / Q000187:drug effects / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D051745:Protein Kinase C-delta / Q000378:metabolism*
D000098:Acetophenones; D000199:Actins; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D005609:Free Radicals; D007211:Indoles; D008301:Maleimides; C085746:rottlerin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D051745:Protein Kinase C-delta; C070515:bisindolylmaleimide I