THE ROLE OF G-PROTEINS IN THE ACTIVATION OF HUMAN-LEUKOCYTES BY PARTICULATE STIMULI TO PRODUCE REACTIVE OXYGEN METABOLITES

Effects of pertussis toxin (PTX), cholera toxin (CTX) and an anhydroly zable GTP analogue, GTP gamma S, on the levels of free intracellular c alcium ([Ca2+](i)) and the production of reactive oxygen metabolites ( ROM) in human polymorphonuclear leukocytes (PMNL) were studied during cell activation. Cells were stimulated by particulate stimuli, quartz or chrysotile, and soluble stimuli, formyl-methionyl-leucyl-phenylalan ine (fMLP) or phorbol myristate acetate (PMA). Pretreatment of PMNL wi th PTX decreased fMLP-induced elevations of [Ca2+](i) but not those in duced by quartz or chrysotile. CTX, in turn, decreased both quartz- an d fMLP-induced elevations of [Ca2+](i). Likewise, PTX inhibited only f MLP-induced production of ROM, whereas CTX inhibited also those induce d by quartz, chrysotile or fMLP. PIX or CTX did not, however, have an impact on PMA-induced production of ROM. GTP gamma S alone did not ele vate [Ca2+](i) or amplify fMLP-, quartz- or chrysotile-induced [Ca2+]( i) elevation. However, GTP gamma S alone increased the production of R OM and amplified ROM production induced by fMLP and quartz. The presen t results suggest that a CTX-sensitive G-protein may be involved in qu artz-induced PMNL activation whereas an fMLP-induced neutrophil activa tion may be regulated by G-proteins sensitive to both PTX and CTX. The involvement of G-protein in chrysotile-induced leukocyte activation i s not likely. There may be, however, a relationship between G-protein- mediated cell signalling and quartz-induced production of reactive oxy gen metabolites in these cells.