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. 1987 Jan;79(1):179–187. doi: 10.1172/JCI112781

Studies on the mechanism of omega-hydroxylation of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) by unstimulated neutrophils.

A J Marcus, L B Safier, H L Ullman, N Islam, M J Broekman, C von Schacky
PMCID: PMC424017  PMID: 3025259

Abstract

Stimulated platelets, in the presence or absence of aspirin, synthesize significant quantities of 12-hydroxyeicosatetraenoic acid (12-HETE), which is chemotactic and chemokinetic, and enhances mononuclear cell procoagulant activity. During a cell-cell interaction between stimulated platelets and unstimulated neutrophils, platelet 12-HETE is metabolized to 12,20-dihydroxyeicosatetraenoic acid (12,20-DiHETE) by neutrophils. Characteristics of the enzyme system in unstimulated neutrophils responsible for this omega-hydroxylation were investigated. A broad range of cytochrome P-450 inhibitors, as well as leukotriene B4, blocked formation of 12,20-DiHETE. Owing largely to released proteases, neutrophil homogenization abolished activity. Pretreatment with diisopropylfluorophosphate preserved activity in neutrophil homogenates. omega-Hydroxylation of 12-HETE was confined solely to the microsomal fraction. Specific activity increased 6.6-fold compared with neutrophil sonicates. The electron donor NADPH was a required cofactor. These results indicate that the enzyme in unstimulated human neutrophils, which metabolizes 12-HETE from stimulated platelets to 12,20-DiHETE in this cell-cell interaction, is a cytochrome P-450 monooxygenase.

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Selected References

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