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

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Abstract
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, agarose column chromatography, electrophoretic and immunochemical techniques, and electron microscopy. Some experiments used apo A-I, apo A-II, or Triton labeled with either 125I or 131I. At concentrations of less than 10 mg/ml plasma, Triton interacted preferentially with HDL, changing lipoprotein size and density; Triton was progressively incorporated into the HDL particles, displacing apo E, apo A-I, and apo A-II. At concentrations above 10 mg/ml plasma, Triton displaced all apo A-I from the particle, and much lipid was dissolved into the Triton micelles. When Triton-treated HDL particles were used as a substrate for the enzyme LCAT, enzyme activity decreased in parallel to the displacement of apo A-I. 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-I disappeared rapidly from the circulation; 125I apo A-II disappeared less rapidly. These increased clearances were accompanied by a drop in apo A-I 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 concentrations, Triton acts on surface components of the HDL particle; at higher concentrations, 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-function relationships.