TY - JOUR
T1 - 12(R)-hydroxyeicosatrienoic acid, a potent chemotactic and angiogenic factor produced by the cornea
AU - Masferrer, Jaime L.
AU - Rimarachin, Julio A.
AU - Gerritsen, Mary E.
AU - Falck, J R
AU - Yadagiri, P.
AU - Dunn, Michael W.
AU - Laniado-Schwartzman, Michal
N1 - Funding Information:
This work was supported by NIH Grants EYCl6153 (M.L.S.),EY06998 (M.E.G.),andGM31278 (J.R.F.). J.L.M. is a recipiento f the R. Townley Paton Fellowshipf rom the New York Bank for Sight Restoration,I nc. and ML. S. is a recipiento f the Irma T. Hirsch1C areerS cientistA ward. The author wishest o thankJ enniferJ ones for her assistance in the preparationo f the manuscript.
PY - 1991/4
Y1 - 1991/4
N2 - 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 vasodilation 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 μg of compound DR. In contrast, the stereoisomer DS at the same concentration (0·5 μg) 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 10-11m, 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.
AB - 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 vasodilation 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 μg of compound DR. In contrast, the stereoisomer DS at the same concentration (0·5 μg) 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 10-11m, 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.
KW - angiogenesis
KW - arachidonic acid
KW - chemotaxis
KW - corneal
KW - cytochrome P450
KW - epithelium
UR - http://www.scopus.com/inward/record.url?scp=0025760107&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025760107&partnerID=8YFLogxK
U2 - 10.1016/0014-4835(91)90037-F
DO - 10.1016/0014-4835(91)90037-F
M3 - Article
C2 - 1709873
AN - SCOPUS:0025760107
SN - 0014-4835
VL - 52
SP - 417
EP - 424
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 4
ER -