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6‐Trans‐Leukotriene B 4 Is a Neutrophil Chemotaxin in the Guinea Pig Dermis
Author(s) -
Fretland Donald J.,
Widomski Deborah L.,
Anglin Charles P.,
Walsh Robin E.,
Levin Stuart,
Gaginella Timothy S.
Publication year - 1991
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.49.3.283
Subject(s) - leukotriene b4 , leukotriene , proinflammatory cytokine , biology , guinea pig , arachidonic acid , dermis , arachidonate 5 lipoxygenase , granulocyte , immunology , lipoxygenase , chemotaxis , inflammation , receptor , pharmacology , biochemistry , enzyme , endocrinology , anatomy , asthma
The products of the 5‐ and 12‐lipoxygenase (5‐LO, 12‐LO) pathways of arachidonic acid metabolism are implicated as proinflammatory mediators in a number of disease states. 12(R)‐hydroxyeicosatetraenoic acid [12(R)‐HETE] is present in large quantities in human psoriatic lesional skin and can be further metabolized by 5‐LO to 5(S),12(R)‐dihydroxy‐(6E,8Z,10E,14Z)‐eicosatetraenoic acid (6‐trans‐LTB 4 ). Furthermore, leukotriene B 4 (LTB 4 ) and the sulfidopeptide leukotrienes (LTC 4 , LTD 4 ) can be transformed to 6‐trans‐LTB 4 . When injected into the guinea pig dermis, 6‐trans‐LTB 4 (1.0,10.0,20.0 μg/intradermal site) caused a significant ( P < 0.02) infiltration of polymorphonuclear leukocytes (PMN) at 4 hr as assessed by histology and the levels of the PMN marker enzyme myeloperoxidase. 6‐Trans‐LTB 4 is a more potent PMN chemoattractant than 12(R)‐HETE in the guinea pig dermis but is far less potent than LTB 4 . Pharmacological interdiction of leukotriene production or receptor binding should take into account the proinflammatory activity of 6‐trans‐LTB 4 .
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