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Effects of a protein kinase C inhibitor, Ro 31-7549, on the activation of human leuko cytes 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 pro duce 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 intracellu lar 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 results suggest that PKC may have an important role in the activation of PMNL to produce ROM by par ticulate 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-depen dent and -independent mechanisms may play a role in the activation of human leukocytes to produce ROM.