TRIGLYCERIDE TRANSFER IS REQUIRED FOR NET CHOLESTERYL ESTER TRANSFER BETWEEN LIPOPROTEINS IN PLASMA BY LIPID TRANSFER PROTEIN - EVIDENCE FOR A HETERO-EXCHANGE TRANSFER MECHANISM DEMONSTRATED BY USING NOVEL MONOCLONAL-ANTIBODIES

In order to investigate the role of lipid transfer protein (LTP) in pl asma lipoprotein metabolism, monoclonal antibodies (mAbs) have been ra ised against LTP isolated from rabbit plasma. mAbs 2-8G and 3-9F inhib ited both [H-3]cholesteryl ester (CE) and [H-3]triglyceride (TG) trans fer from low density lipoprotein (LDL) to high density lipoprotein (HD L) mediated by LTP. Although 3-9F cross-reacted with human LTP, 2-8G w as species specific for rabbit LTP. mAb 14-8H inhibited only [H-3]TG b ut not [H-3]CE transfer and was cross-reactive with human LTP. mAbs 2- 8G and 3-9F interfered with association of LTP with lipid microemulsio ns, again 2-8G with species specificity, whereas 14-8H did not affect LTP-microemulsion binding. Thus, mAbs 3-9F and 14-8H were used for fur ther study in human plasma. By total inhibition of CE and TG transfer by 3-9F, LTP was shown to be responsible for net mass transfer of neut ral Lipids between Lipoprotein classes in plasma, namely of CE from HD L to very low density lipoprotein (VLDL) and TG from VLDL to LDL and H DL. Selective inhibition of TG transfer by mAb 14-8H was also able to inhibit such net neutral lipid transfer. Such effect of these antibodi es was demonstrated more remarkably in the presence of cholesterol est erification. Thus, TG transfer activity of LTP was shown to be require d for net CE transfer, suggesting that net neutral Lipid transfer in p lasma between lipoproteins occurred mainly by a hetero-exchange mechan ism. Inhibition of net neutral lipid transfer in plasma did not affect cholesterol esterification occurring predominantly on HDL. Consequent ly, mAb inhibition of TG transfer in plasma leads to CE accumulation i n HDL. It is possible that hyperalphalipoproteinemia may be induced by a mutation in LTP that causes a selective defect in TG transfer activ ity.