12(R)-hydroxyeicosatetraenoic acid is a neutrophil chemoattractant in the cavine, lapine, murine and canine dermis.
Psoriasis is a disease state characterized by epidermal proliferation, neutrophil infiltration, along with release of the proinflammatory mediators leukotriene-B4(LTB4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE]. LTB4 and 12(R)-HETE are chemoattractant to the neutrophil, the latter approximately 1000x less potent. LTB4 and 12(R)-HETE are present in psoriatic scale, the latter in quantities so much greater than LTB4 that it is proposed as a primary mediator of neutrophil infiltration in psoriasis. 12(R)-HETE, synthesized in optically pure form by a new, shorter route, was injected into the dermis of the cavine, lapine, canine, mouse and rat. At doses up to 50 mu gm per intradermal site, 12(R)-HETE was chemoattractant to the neutrophil (as assessed by dermal myeloperoxidase levels) with response in the cavine greater than canine greater than lapine greater than mouse greater than rat.
Fretland
D J
DJ
Gastrointestinal Diseases Research Department, G.D. Searle and Co., Skokie, Illinois 60077.
Widomski
D L
DL
Zemaitis
J M
JM
Tsai
B S
BS
Djuric
S W
SW
Penning
T D
TD
Miyashiro
J M
JM
Bauer
R F
RF
D000818:Animals; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012867:Skin / Q000187:drug effects*
D002630:Chemotactic Factors; D006893:Hydroxyeicosatetraenoic Acids; D009195:Peroxidase