Chrysotile asbestos-induced cytotoxicity and calcium-dependent exocytosis in polymorphonuclear leukocytes.
Chrysotile asbestos is cytotoxic for rabbit polymorphonuclear leukocytes (PMNs) which is evident from the release of the cytoplasmic enzyme LDH. In the presence of Ca2+, but not in its absence, a strong lysozyme release occurs. High concentrations of Ca2+ are required for exocytosis. In the presence of the stable guanine nucleotide GTP gamma S exocytosis occurs at lower Ca2+ concentrations. The results suggest that the plasma membrane is permeabilized by asbestos, allowing the influx of extracellular Ca2+ which causes exocytosis. At high Ca2+ concentrations asbestos-induced cytotoxicity is strongly reduced. The cytotoxic LDH release and, to a lesser degree, the exocytotic enzyme release are inhibited by Co2+, Mn2+ and La3+. Cytochalasin B and the glycolytic inhibitors 2-deoxyglucose and iodoacetate inhibit asbestos-induced cytotoxicity, indicating that microfilaments and glycolytic energy are required for the membrane-damaging actions of asbestos.
Elferink
J G
JG
Department of Medical Biochemistry, Sylvius Laboratories, University of Leiden, The Netherlands.
D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D017632:Asbestos, Serpentine; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects*; D003571:Cytochalasin B / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology; D004533:Egtazic Acid / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011817:Rabbits; D013873:Thionucleotides / Q000494:pharmacology
D017632:Asbestos, Serpentine; D013873:Thionucleotides; D001194:Asbestos; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003571:Cytochalasin B; D004533:Egtazic Acid; D006160:Guanosine Triphosphate; D007770:L-Lactate Dehydrogenase; D009113:Muramidase; D002118:Calcium