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Effects of a protein kinase C inhibitor, Ro 31-7549, on the activation of human leuko cytes by particulate stimuli

National Public Health Institute, Department of Toxicology, PO Box 95, FIN-70701 Kuopio, Finland

Kai M Savolainen

National Public Health Institute, Department of Toxicology, PO Box 95, FIN-70701 Kuopio, Finland

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.

Key Words: leukocyte activation • free intracellular calcium • protein kinase C • reactive oxygen metabolites • mineral fibers

Human & Experimental Toxicology, Vol. 14, No. 3, 266-272 (1995)
DOI: 10.1177/096032719501400306


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