Inhibition of production of LTB4 and chemotactic agent from rat alveolar macrophages treated with t-butyl hydroperoxide is independent of ATP depletion.
In rat alveolar macrophages treated with 100 microM t-butyl hydroperoxide (tBOOH), leukotriene B4 (LTB4) synthesis was significantly lower than the basal level while levels of cyclooxygenase pathway products were increased. LTB4, 5,6-dihydroxyeicosatetraenoic acid (5,6-DiHETEs), and 5-hydroxyeicosatetraenoic acid (5-HETE) production in macrophages was significantly stimulated by 2 microM A23187, but this was suppressed 40% by simultaneous addition of 10 microM tBOOH and completely abolished by 100 microM tBOOH. Basal and A23187-stimulated macrophage production of chemotactic agents were similarly suppressed by addition of tBOOH; this effect paralleled depression of cellular LTB4 synthesis. In contrast to the significant depression of A23187-stimulated formation of 5-lipoxygenase products by 10 microM tBOOH, cellular adenosine triphosphate (ATP) was unchanged. Macrophages pretreated with KCN led to a 42% decline in ATP levels; however, LTB4, 5,6-DiHETEs, and 5-HETE production in response to A23187 was not suppressed. The results indicate that inhibition of 5-lipoxygenase pathway products in macrophages treated with tBOOH did not occur by depletion of cellular ATP levels.
Robison
T W
TW
Department of Pediatrics, University of Southern California, Childrens Hospital of Los Angeles 90027-0700.
Duncan
D P
DP
Coates
T D
TD
Forman
H J
HJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000302:isolation & purification / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D010545:Peroxides; D007975:Leukotriene B4; D000001:Calcimycin; D000255:Adenosine Triphosphate; D020122:tert-Butylhydroperoxide