In vitro and in vivo interactions of Triton 1339 with plasma lipoproteins of normolipidemic rhesus monkeys. Preferential effects on high density lipoproteins. Arteriosclerosis

Triton WR-1339 was incubated in vitro in various proportions with plasma from normolipidemic rhesus monkeys or with ultracentrifugally purified lipoproteins, and the products were examined by isopycnic density gradient ultracentrifugation, aga-rose column chromatography, electrophoretic and immunochemical techniques, and electron microscopy. Some experiments used apo A-l, apo A-ll, or Triton labeled with either 125I or 1 3 1 I. At concentrations of less than 10 mg/ml plasma, Triton interacted preferentially with HDL, changing lipoprotein size and density; Triton was progres-sively incorporated into the HDL particles, displacing apo E, apo A-l, and apo A-ll. At concentrations above 10 mg/ml plasma, Triton displaced all apo A-l from the particle, and much lipid was dissolved into the Triton micelles. When Triton-treated HDL parti-cles were used as a substrate for the enzyme LCAT, enzyme activity decreased in parallel to the displacement of apo A-l. There was no displacement of apo B from LDL nor any loss of lipids; but the particles became deformed and formed rouleaux. A single intravenous dose of Triton WR-1339 administered to a normolipidemic monkey (N) and to a hypercholesterolemic monkey (H) resulted in concentration-dependent HDL changes similar to those observed in vitro. LDL was less affected by Triton, with changes occurring only at high doses. After these structural changes, intravenously injected 131I apo A-l disappeared rapidly from the circulation; 125I apo A-II disappeared less rapidly. These increased clearances were accompanied by a drop in apo A-l plasma levels and the disappearance of HDL particles from plasma. The lipoprotein and apolipoprotein patterns returned to normal 14 days after Triton. We conclude that Triton WR-1339, when exposed to rhesus plasma in vitro or in vivo, interacts preferentially with HDL in a dose-dependent manner. At low concentra-tions, Triton acts on surface components of the HDL particle; at higher concentra-tions, Triton penetrates the particle, causing structural disruption. Because of its high affinity for HDL, Triton WR-1339 is a useful reagent for study of HDL structure-functio