Effect of ozone on platelet activating factor metabolism in phorbol-differentiated HL60 cells.
The mechanisms of ozone (O3) toxicity in the lung may involve the formation of lipid inflammatory mediators. We have previously demonstrated that exposure to O3 in vitro results in increased accumulation and release of platelet activating factor (PAF) in the macrophage-like cell line HL60 differentiated with phorbol ester (dHL60). In the present study we have examined possible biochemical mechanisms responsible for the O3-induced increase in PAF levels in dHL60 cells. Specifically, we studied the effect of O3 on phospholipase A2 (PLA2), acetyltransferase, acetylhydrolase, and reacylation activities. dHL60 cells were exposed to 1.0 ppm O3 or air alone. O3 exposure was found to significantly decrease dHL60 cell acetylhydrolase activity by 36%. Additional experiments demonstrated that extracellular acetylhydrolase activity, but not intracellular acetylhydrolase activity, was inhibited by O3 exposure of dHL60 cells. O3 exposure resulted in a small (13%) but statistically significant reduction in reacylation activity in dHL60 cells. In addition, a significant (22%) contribution of PLA2 activation to the O3-induced increase in PAF levels was also found. Basal and calcium ionophore-induced acetyltransferase activity was found to be unaffected by exposure of dHL60 cells to O3. These data suggest that in vitro exposure to O3 affects both synthetic and degradative pathways of PAF metabolism in dHL60 cells.
Samet
J M
JM
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599.
Friedman
M
M
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D007942:Leukemia, Experimental / Q000201:enzymology / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000378:metabolism*; D010126:Ozone / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D010972:Platelet Activating Factor; D010126:Ozone; D000123:Acetyltransferases; D006867:Hydrolases; D010741:Phospholipases A; D054467:Phospholipases A2