UPTAKE OF CHYLOMICRONS BY THE LIVER, BUT NOT BY THE BONE-MARROW, IS MODULATED BY LIPOPROTEIN-LIPASE ACTIVITY

We have shown that chylomicrons are catabolized by the liver and bone marrow in rabbits and marmosets. In the present investigation, we stud ied the role of various apolipoproteins and lipoprotein lipase in the clearance of these particles by the liver and bone marrow in rabbits. Incubation of chylomicrons with purified apolipoprotein (ape) E or C-I I resulted in more rapid clearance of these particles from the plasma, whereas incubation of chylomicrons with apoA-I, apoC-I, apoC-III1, or apoC-III2 did not affect their clearance rates. Analysis of tissue up take revealed that the increased plasma clearance rate of chylomicrons enriched with apoE or apoC-II was primarily due to enhanced uptake by the liver. The uptake of chylomicrons by the bone marrow increased af ter their enrichment with apoA-I but decreased after their enrichment with apoC-II. Because apoC-II is a cofactor for lipoprotein lipase, we hypothesized that the increased clearance rates were due to faster hy drolysis of chylomicrons and rapid generation of chylomicron remnants. To test this hypothesis, lipoprotein lipase activity was inhibited by injection of an antilipoprotein lipase monoclonal antibody. Inhibitio n of lipoprotein lipase retarded clearance of chylomicrons from the pl asma and decreased their uptake by the liver but did not affect their uptake by the bone marrow. These studies suggest that bone Marrow can take up chylomicrons in the absence of lipoprotein lipase activity and provide an explanation for the presence of foam cells in the bone mar row of type I hyperlipoproteinemic patients.