6-trans-leukotriene B4 is a neutrophil chemotaxin in the guinea pig dermis.
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-LTB4). Furthermore, leukotriene B4 (LTB4) and the sulfidopeptide leukotrienes (LTC4, LTD4) can be transformed to 6-trans-LTB4. When injected into the guinea pig dermis, 6-trans-LTB4 (1.0, 10.0, 20.0 micrograms/intradermal site) caused a significant (P less than 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-LTB4 is a more potent PMN chemoattractant than 12(R)-HETE in the guinea pig dermis but is far less potent than LTB4. Pharmacological interdiction of leukotriene production or receptor binding should take into account the proinflammatory activity of 6-trans-LTB4.
Fretland
D J
DJ
Gastrointestinal Diseases Research, G.D. Searle and Co., Skokie, Illinois 60077.
Widomski
D L
DL
Anglin
C P
CP
Walsh
R E
RE
Levin
S
S
Gaginella
T S
TS
D000818:Animals; D002630:Chemotactic Factors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007975:Leukotriene B4 / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena
D002630:Chemotactic Factors; D007975:Leukotriene B4; D009195:Peroxidase