Conversion of 5,6-dihydroxyeicosatetraenoic acids. A novel pathway for lipoxin formation by human platelets.
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.
Tornhamre
S
S
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Gigou
A
A
Edenius
C
C
Lellouche
J P
JP
Lindgren
J A
JA
D001792:Blood Platelets / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D015289:Leukotrienes / Q000378:metabolism; D044045:Lipoxins; D008084:Lipoxygenase / Q000378:metabolism
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D044045:Lipoxins; C040527:lipoxin A4; D000001:Calcimycin; C048698:5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid; D008084:Lipoxygenase