BIOSYNTHESIS OF SULFIDOPEPTIDE LEUKOTRIENES VIA THE TRANSFER OF LEUKOTRIENE A(4) FROM POLYMORPHONUCLEAR CELLS TO BOVINE RETINAL PERICYTES

Administration of exogenous sulfidopeptide leukotrienes (LTs) is assoc iated with enhanced microvascular permeability. In addition, endogenou s LTs have been implicated as participants in permeability (nonhydrost atic) edema formation. The source of LTs for interaction with the micr ovasculature is, however, unknown. We hypothesized that pericytes cont ribute to vascular LT synthesis. Under basal conditions and after incu bation with either the calcium ionophore, A23187 (0-1 mu M), or arachi donic acid (20 mu M), bovine retinal pericytes (BRPs) did not produce significant amounts of sulfidopeptide LTs. In contrast, in the presenc e of polymorphonuclear leukocytes (PMNs), which can synthesize LTA(4), but not sulfidopeptide leukotrienes, incubation of BRPs with A23187 r esulted in dose-dependent increases in LTC4/D-4/E-4 production (peak: 35.4+/-5 pg/mu g protein; n = 12). Similarly, BRPs, incubated with exo genous, authentic LTA(4) (10 mu M), synthesized sulfidopeptide LTs (pe ak: 18.9 +/- 5 pg/mu g protein, n = 3). Preincubation (30 min) of BRPs with PMNs and the lipoxygenase inhibitor, esculetin (1 x 10(-4) M; n = 12), reduced peak A23187-induced production of LTs by 63.9 +/- 7%. F inally, Northern blot analysis revealed mRNA for 5-lipoxygenase to be present in human and bovine PMNs, but not in BRPs. These results sugge st that pericytes produce sulfidopeptide LTs only when provided with L TA(4) from an external source such as the PMN. Interactions between pe ricytes and PMNs may lead to the production of sulfidopeptide LTs, whi ch, in turn, could alter microvascular permeability.