Chemotactic response to some arachidonic acid lipoxygenase products in the rabbit eye

The effects of arachidonic acid, its cyclo-oxygenase and lipoxygenase products and the synthetic chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) on leukocyte accumulation in the aqueous humour and intraocular pressure in the rabbit were studied in vivo. Substances were injected into the anterior chamber of the eyes of anaesthetised rabbits using a closed circuit perfusion system. Injection of arachidonic acid, prostaglandins E1 and E2, and the monohydroperoxy and hydroxy acids of the lipoxygenase pathway did not result in any significant accumulation of leukocytes in the anterior chamber. In contrast, FMLP and 5,12-diHETE (Leukotrine B4) resulted in significant dose dependent accumulation of leukocytes into the aqueous humour. Leukocytes appeared in the aqueous humour between 2 and 3 h after the injection of either FMLP or LTB4 and the response was maximal at 4 h. None of the lipoxygenase products tested had any effect on intraocular pressure in contrast to the profound effects observed with arachidonic acid and the E type prostaglandins. FMLP had a small but significant effect on intraocular pressure at the highest dose tested for leukocyte accumulation. These results indicate that the effects of the cyclo-oxygenase products of arachidonate metabolism are mainly vascular in the rabbit eye in contrast to the predominantly cellular effects of lipoxygenase products. Thus in the eye, the interaction of cyclo-oxygenase and lipoxygenase products of arachidonate metabolism may be important in the development of both acute and chronic ocular inflammation.