Increased synthesis of specific eicosanoids in rejected corneal grafts.
OBJECTIVE
Corneal injury stimulates the formation of both prostaglandins (PG) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), the major lipoxygenase metabolite. The purpose of this study was to investigate the metabolism of arachidonic acid (AA) in a model of corneal graft rejection.


METHODS
Corneal tissue from Dutch belted rabbits was transplanted to vascularized corneas of New Zealand white rabbits. Rejected corneas were removed at the endstage of allograft failure. The allograft, the host corneal rim, the contralateral control cornea rim of equal size and normal Dutch belted cornea from the same site as the allograft were incubated with 0.25 microCi [3H]AA and the released eicosanoids were analyzed by high-performance liquid chromatography.


RESULTS
The host corneal rims, adjacent to the failed allografts, produced up to five times as much 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) as contralateral control corneal rims. Additionally, prostaglandin E2 (PGE2) formation in the host rims increased 100% above controls, and 12(S)-HETE and PGE2 synthesis in the rejected corneal graft also increased. 12(R)-HETrE, an endogenous corneal angiogenic factor, was not detected in rejected corneas.


CONCLUSIONS
The results point to the importance of selective AA pathways as the source key inflammatory components found in rejected allografts.
Lin
N
N
LSU Eye Center, Louisiana State University Medical Center, School of Medicine, New Orleans 70112, USA.
Hurst
J
J
Bazan
H E
HE
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D016039:Corneal Transplantation; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis*; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D011817:Rabbits
D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015232:Dinoprostone