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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1407-1413.)
© 1997 American Heart Association, Inc.

Articles

Uptake of Chylomicrons by the Liver, but Not by the Bone Marrow, Is Modulated by Lipoprotein Lipase Activity

M. Mahmood Hussain; Ira J. Goldberg; Karl H. Weisgraber; Robert W. Mahley; ; Thomas L. Innerarity

From the Gladstone Institute of Cardiovascular Disease (M.M.H., K.H.W., R.W.M., T.L.I.), the Departments of Pathology (K.H.W., R.W.M., T.L.I.) and Medicine (R.W.M.), and the Cardiovascular Research Institute (M.M.H., K.H.W., R.W.M., T.L.I.), University of California, San Francisco; and the Department of Medicine, College of Physicians & Surgeons of Columbia University, New York, NY (I.J.G.).

Correspondence to Thomas L. Innerarity, PhD, Gladstone Institute of Cardiovascular Disease, PO Box 419100, San Francisco, CA 94141-9100.

Abstract We have shown that chylomicrons are catabolized by the liver and bone marrow in rabbits and marmosets. In the present investigation, we studied 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 (apo) E or C-II 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 uptake 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 after 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 hydrolysis of chylomicrons and rapid generation of chylomicron remnants. To test this hypothesis, lipoprotein lipase activity was inhibited by injection of an anti–lipoprotein lipase monoclonal antibody. Inhibition of lipoprotein lipase retarded clearance of chylomicrons from the plasma 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 marrow of type I hyperlipoproteinemic patients.

Key Words: apolipoproteins • lipoproteins • apoE • apoC-II • apoA-I

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