Role of extracellular calcium in chrysotile asbestos stimulation of alveolar macrophages.
The purpose of these studies was to determine whether extracellular calcium and calcium channels can influence chrysotile asbestos-stimulated production of superoxide anion by guinea pig alveolar macrophages. Increasing the extracellular calcium concentration from 0.0 to 10.0 mM markedly enhanced the ability of noncytotoxic levels of chrysotile (25 micrograms/ml) to stimulate macrophage production of superoxide anion at 37 degrees C. The primary effect of increasing extracellular calcium was to prolong superoxide anion production. In parallel with these calcium-dependent effects on superoxide anion production, chrysotile also caused an elevation of cytosolic calcium (measured using Fura-2) which increased with increasing extracellular calcium concentrations. A number of organic calcium channel antagonists were tested for their ability to block chrysotile-stimulated superoxide anion production by cells in medium containing physiological levels of calcium. The relative order of potency of these antagonists was verapamil much greater than nimopidine approximately diltiazem approximately nifedipine greater than segontin. In parallel with its effects on superoxide anion production, verapamil also partially blocked the observed chrysotile-stimulated elevation of cytosolic calcium. Taken together, these results suggest that chrysotile can open calcium channels on the macrophage surface, allowing extracellular calcium to enter and contribute to the elevation of cytosolic calcium levels. This elevation of cytosolic calcium in turn serves to prolong chrysotile-stimulated superoxide anion production.
Kalla
B
B
Department of Internal Medicine, University of Texas Medical School, Houston 77030.
Hamilton
R F
RF
Scheule
R K
RK
Holian
A
A
D000818:Animals; D001194:Asbestos / Q000494:pharmacology*; D017632:Asbestos, Serpentine; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology; D013481:Superoxides / Q000378:metabolism
D017632:Asbestos, Serpentine; D002121:Calcium Channel Blockers; D013481:Superoxides; D001194:Asbestos; D002118:Calcium