4-HYDROXYNONENAL INDUCES MEMBRANE PERTURBATIONS AND INHIBITION OF BASAL PROSTACYCLIN PRODUCTION IN ENDOTHELIAL-CELLS, AND MIGRATION OF MONOCYTES

Cultured bovine aortic endothelial cells (BAEC) were incubated for 5 d ays with 10(-5) 4-hydroxynonenal (HN). HN treated BAEC and controls we re either (i) further incubated with I-125-polymyxin B (IPxB) or with radioiodinated, inactivated coagulation factor Xa (IFXai) as markers o f membrane phospholipid perturbation, or (ii) assayed for the synthesi s of prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)). Rabbit blood mononuclear cells enriched in monocytes (MC) were isolated and assaye d for chemotactic response to HN. The results showed six-fold increase s of IPxB and IFXai binding to BAEC treated with HN, as compared to un treated controls. We also found in HN treated cells a marked inhibitio n of PGI(2) synthesis, but an unmodified TXA(2) production. In additio n, HN in the 10(-5)-10(-10) M range induced oriented migration of MC.