Effects of a protein kinase C inhibitor, Ro 31-7549, on the activation of human leukocytes by particulate stimuli.
1. A new specific protein kinase C (PKC) inhibitor, Ro 31-7549, was used to explore the mechanisms by which particulate stimuli, quartz and chrysotile, stimulate human polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM). Also soluble stimuli, formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and phorbol myristate acetate (PMA) were used. 2. Ro 31-7549 inhibited chrysotile-induced free intracellular calcium ([Ca2+]i) elevations but did not have an effect on quartz-induced elevations of [Ca2+]i. Both quartz and chrysotile induced production of ROM were partially inhibited by Ro 31-7549. fMLP-induced elevation of [Ca2+]i was inhibited by Ro 31-7549 whereas PMA did not affect [Ca2+]i. Ro 31-7549 strongly inhibited fMLP-induced ROM production, and completely abolished that induced by PMA. 3. These result suggest that PKC may have an important role in the activation of PMNL to produce ROM by particulate and soluble stimuli. However, the inhibition of chrysotile-, but not of quartz-induced [Ca2+]i elevations by Ro 31-7549 provides evidence that both PKC-dependent and -independent mechanisms may play a role in the activation of human leukocytes to produce ROM.
Ruotsalainen
M
M
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Savolainen
K M
KM
D000328:Adult; D017632:Asbestos, Serpentine / Q000378:metabolism; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011791:Quartz / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D017632:Asbestos, Serpentine; D007211:Indoles; D008301:Maleimides; D017382:Reactive Oxygen Species; D011791:Quartz; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C064755:Ro 31-7549