Changes in free intracellular calcium and production of reactive oxygen metabolites in human leukocytes by soluble and particulate stimuli.
Changes in free intracellular calcium concentration ([Ca2+]i) and in the production of reactive oxygen metabolites (ROM) were studied in human polymorphonuclear leukocytes (PMNL) exposed to graded concentrations of formyl-methionyl-leucyl-phenylalanine (fMLP), a chemotactic peptide, phorbol myristate acetate (PMA), a stimulator of protein kinase C (PKC), quartz, or chrysotile. fMLP, quartz, and chrysotile induced a concentration-dependent elevation in [Ca2+]i. PMA did not affect [Ca2+]i. fMLP caused a rapid and transient increase in [Ca2+]i, whereas that caused by quartz or chrysotile was slow and sustained. fMLP, PMA and quartz all caused a concentration-dependent ROM production in PMNL. Chrysotile also caused a concentration-dependent increase in ROM production, but the slope of the curve was more gentle, with the maximum response being only 25% of that caused by the other stimuli. fMLP caused a rapid and transient peak in ROM production at 5 min, PMA a peak at 15 min, whereas quartz and chrysotile induced a biphasic ROM production with peaks at 5 and 20 min, and at 18 and 28 min, respectively. These results suggest that [Ca2+]i may have an important role in the production of ROM by PMNL after an exposure to fMLP, quartz, or chrysotile, and that the involvement of PKC in ROM production is possible.
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
M
M
Tuomala
M R
MR
Hirvonen
K M
KM
Savolainen
D001194:Asbestos / Q000494:pharmacology; D017632:Asbestos, Serpentine; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011791:Quartz / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017632:Asbestos, Serpentine; D017382:Reactive Oxygen Species; D001194:Asbestos; D011791:Quartz; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium