12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid is a more potent neutrophil chemoattractant than the 12(R) epimer in the rat cornea.
12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE] is reported to be more potent than its epimer 12(S)-HETE as a chemoattractant for human neutrophils in vitro and following topical application to the skin. To assess the in vivo neutrophil chemoattractant potencies of 12(S)-HETE and 12(R)-HETE in the rat, we injected 1 microgram, 5 micrograms, or 10 micrograms of these eicosanoids into the corneal stroma. Rats were killed 12-15 hours after injection, and the number of neutrophils in the stroma was counted in a histological section of the cornea including the injection site. The number of neutrophils was significantly increased in corneas injected with 5 micrograms (+103% of control) or 10 micrograms (+456% of control) of 12(S)-HETE and in those injected with 10 micrograms of 12(R)-HETE (+111% of control). The neutrophilic infiltrate in corneas injected with 1 microgram or 5 micrograms of 12(S)-HETE was not significantly different from that in corneas injected with 1 microgram of leukotriene B4. The data for the 10 micrograms injections indicate that 12(S)-HETE is a more potent neutrophil chemoattractant than 12(R)-HETE in the rat cornea. Our results suggest that species or tissue specificity may determine the relative potencies of 12-HETE epimers as chemoattractants for neutrophils, and that 12(S)-HETE may be an important inflammatory mediator in the rat cornea.
Wiggins
R E
RE
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
Jafri
M S
MS
Proia
A D
AD
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D002634:Chemotaxis, Leukocyte; D003315:Cornea / Q000166:cytology* / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004848:Epithelium / Q000033:anatomy & histology; D006893:Hydroxyeicosatetraenoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007975:Leukotriene B4 / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D004121:Dimethyl Sulfoxide