Conversion of 5, 6‐dihydroxyeicosatetraenoic acids A novel pathway for lipoxin formation by human platelets

S Tornhamre, A Gigou, C Edenius, J. P Lellouche, J. Å Lindgren

Research output: Contribution to journalArticlepeer-review

Abstract

Leukotriene A4 may be metabolized to 5(S),6(R)- and 5(S),6(S)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids by enzymatic or non-enzymatic hydrolysis. Incubation of human platelet suspensions with these dihydroxy acids led to the formation of lipoxin A4 and 6(S)-lipoxin A4 via lipoxygenation at C-15. Furthermore, human platelets converted the two 5(R),6(S)- and 5(R),6(R)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids to tetraene-containing trihydroxyeicosatetraenoic acids. In contrast, leukotrienes C4, D4 and E4 were not transformed to cysteinyl-lipoxins, Time-course studies of leukotriene A4 metabolism in human platelet suspensions indicated lipoxin formation via two pathways: (i) direct conversion of leukotriene A4, leading to formation of the lipoxin intermediate 15-hydroxy-leukotriene A4; and (ii) 15-lipoxygenation of the 5(S),6(R)- and 5(S),6(S)-dihydroxyeicosatetraenoic acids. The results demonstrate that lipoxygenation at C-15 of 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids may be an alternative novel pathway for platelet-dependent lipoxin formation.
Original languageAmerican English
Pages (from-to)78-82
JournalFEBS Letters
Volume304
Issue number1
StatePublished - 1992

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