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Conversion of 5,6‐dihydroxyeicosatetraenoic acids A novel pathway for lipoxin formation by human platelets
Author(s) -
Tornhamre Susanne,
Gigou Agnès,
Edenius Charlotte,
Lellouche Jean-Paul,
Lindgren Jan Åke
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80593-6
Subject(s) - chemistry , lipoxin , leukotriene , platelet , enzyme , leukotriene b4 , biochemistry , lipoxygenase , stereochemistry , receptor , inflammation , immunology , biology , asthma
Leukotriene A 4 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 A 4 and 6(S)‐lipoxin A 4 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 C 4 , D 4 and E 4 were not transformed to cysteinyl‐lipoxins, Time‐course studies of leukotriene A 4 metabolism in human platelet suspensions indicated lipoxin formation via two pathways: (i) direct conversion of leukotriene A 4 , leading to formation of the lipoxin intermediate 15‐hydroxy‐leukotriene A 4 ; 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.