ARACHIDONATE LIPOXYGENASE PRODUCTS AND RENAL ALLOGRAFT REJECTION IN DOGS

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Abstract
The production of 12-hydroxyeicosatetraenoic acid (12-HETE) and leukotriene B4 (LTB4) was studied in renal tissue obtained from renal allografts and normal kidneys of nonimmunosuppressed dogs that had undergone unilateral renal allotransplantation. We have shown that allografted renal cortex undergoing rejection synthesizes significantly greater quantities of 12-HETE than normal or autotransplanted control renal cortex. There was no significant increase in 12-HETE production by allografted medulla undergoing rejection. Production of LTB4 was significantly greater in the rejecting renal cortex compared to control renal cortex but was not different in the rejecting compared to normal renal medulla. Production of 12-HETE and LTB4 was significantly inhibited by the lipoxygenase-cyclooxygenase inhibitor BW755C, suggesting that production of these compounds was enzyme catalyzed. Histologic examination of renal tissue undergoing rejecting revealed varying degrees of tissue destruction and cellular infiltration. These histologic parameters correlated with the magnitude of 12-HETE production in the allografts. Our findings therefore indicate that arachidonate lipoxygenase products are generated in increased amounts by renal cortical tissue undergoing rejection and suggest that these products may be involved in the rejection process.