The effect of lipoproteins on the release of some eicosanoids by stimulated human leukocytes. A possible role in atherogenesis.

Abstract

Changes in eicosanoid generation have been examined in stimulated human peripheral leukocytes incubated with plasma lipoprotein fractions. Leukocytes (2.5 X 10(7) cells/ml, 90% neutrophils) were incubated with physiological concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL). No release of leukotriene B4 (LTB4) or platelet activating factor (PAF) was noted prior to cell stimulation with either calcium ionophore, opsonized zymosan or FMLP. After stimulation with ionophore, LDL led to a 40% enhancement of LTB4 release compared to control incubations while there was no effect on PAF production. HDL caused a small but not significant increase in LTB4 while VLDL had no effect on the release of LTB4. The formation of the other major lipoxygenase product 5-hydroxy-eicosatetraenoic acid (5-HETE) was decreased by 20% following LDL incubation and by more than 50% after VLDL incubation compared to controls. LTB4 release was also enhanced by 27% after incubation with LDL and stimulation with opsonized zymosan. LDL did not cause any increase in superoxide production by leukocytes stimulated with opsonized zymosan or PMA. PGE2 release was stimulated directly in cells incubated with lipoproteins, particularly LDL and VLDL. Oxidised LDL enhanced LTB4 production to an even greater extent than native LDL. The observed enhancement of LTB4 by LDL is not the result of LDL oxidation during incubation, the provision of arachidonic acid substrate by the lipoprotein nor the uptake of cholesterol by the cell. The effect is most likely associated with the binding of LDL to the cell membrane, since LTB4 enhancement was partially blocked by dextran sulphate.(ABSTRACT TRUNCATED AT 250 WORDS)