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Journal of Lipid Research, Vol 37, 197-209, Copyright © 1996 by Lipid Research, Inc.
E de Faria, LG Fong, M Komaromy and AD Cooper
Studies were carried out in mice utilizing inhibitors of several cell
surface molecules to evaluate their relative roles in chylomicron remnant
removal. Anti-LDL receptor antibody inhibited approximately 45% of rapid
remnant removal from plasma, prolonged their half life (63 s to 115 s) and
reduced hepatic uptake by 45%. Receptor-associated protein (RAP) (1
mg/mouse), a high affinity inhibitor of the LDL receptor-related protein
(LRP) and a low affinity inhibitor of the LDL receptor decreased remnant
removal approximately 55%, prolonged the half life from 63 s to 230 s, and
reduced hepatic uptake by 70%. RAP, but not anti-LDL receptor antibody,
inhibited splenic uptake. With both injected together, an incremental
effect was seen; plasma removal decreased 60%, T1/2 increased to 290 s, and
hepatic uptake decreased by 80%. Thus, it is likely that virtually all of
the very rapid removal of remnants from the plasma by the liver requires
the presence of at least one of these members of the LDL receptor family.
Anti-hepatic lipase antibody caused a small but significant delay in
remnant removal from plasma and a larger decrease in hepatic uptake
(22.5%). It doubled adrenal uptake. The anti-hepatic lipase antibody was
not additive with either the anti-LDL receptor antibody or RAP. Anti-rat
hepatic lipase antibody did not inhibit lipolysis by mouse hepatic lipase,
suggesting that lipolysis is not the way hepatic lipase enhances remnant
uptake. Hepatic lipase bound to remnants to a greater degree than it bound
to other lipoproteins. Together these data suggest that hepatic lipase may
serve as a binding site for chylomicron remnants, thereby enhancing their
affinity for the liver surface, and thus removal by the proteins of the LDL
receptor family. Other molecules may also play a role in removal from the
circulation under conditions where the LDL receptor family receptors are
absent or occupied.
ARTICLES
Relative roles of the LDL receptor, the LDL receptor-like protein, and hepatic lipase in chylomicron remnant removal by the liver
Research Institute, Palo Alto Medical Foundation, CA 94305, USA.
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