12(R)-hydroxyeicosatrienoic acid, a potent chemotactic and angiogenic factor produced by the cornea.
Human and bovine corneal epithelial cytochrome P450 convert arachidonic acid to compound D [12(R)-hydroxy-5,8,14(Z,Z,Z)-eicosatrienoic acid], a metabolite with inflammatory properties including vasodilatation and breakdown of the blood-aqueous barrier. Angiogenic properties of the endogenous compound D and the synthetic enantiomers DR and DS were examined using the corneal micropocket technique. The synthetic compound DR was as active as the endogenously formed compound D. Neovascularization of the cornea was found in all the implants containing as little as 0.5 micrograms of compound DR. In contrast, the stereoisomer DS at the same concentration (0.5 micrograms) was inactive. Since angiogenesis can be secondary to a local inflammatory response, we evaluated the effects of compound DR and its stereoisomer DS on human neutrophil chemotaxis by using a modified Boyden chamber technique. DR, but not DS, was found to be a potent chemotactic factor, exhibiting dose-dependent neutrophil chemotaxis with significant responses observed at doses as low as 10(-11) M, a concentration at which leukotriene B4 does not exhibit significant chemotactic activity. Therefore, compound D produced by the cornea may qualify as an intrinsic corneal angiogenic factor which, in association with other inflammatory mechanisms, account for the growth of new vessels in the cornea that appear in chronic inflammation or in the reparative stages of an acute process.
Masferrer
J L
JL
Department of Pharmacology, New York Medical College, Valhalla 10595.
Rimarachin
J A
JA
Gerritsen
M E
ME
Falck
J R
JR
Yadagiri
P
P
Dunn
M W
MW
Laniado-Schwartzman
M
M
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D000818:Animals; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003315:Cornea / Q000098:blood supply / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits
D043925:Angiogenesis Inducing Agents; D002630:Chemotactic Factors; D006893:Hydroxyeicosatetraenoic Acids; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid