Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism.

Cholesteryl ester transfer protein (CETP) promotes in vitro transfer of cholesteryl ester (CE) and triglyceride (TG) between lipoproteins. We studied the function of CETP in vivo in rabbit lipoprotein metabolism using a neutralizing monoclonal antibody (MAb, TP1) to CETP. Rabbits were injected with TP1 (n = 8), or irrelevant MAb or saline (control, n = 8), resulting in an initial 71% inhibition of CETP, which fell to 45% after 48 h. HDL CE rose in the inhibited animals, reaching levels that doubled initial and control values at 48 h (P less than 0.001). HDL TG fell reciprocally, but HDL protein did not change, suggesting a CE for TG exchange. VLDL CE/TG decreased. Rabbits were also given [3H]cholesteryl ether HDL (a CE analogue). CETP inhibition delayed the initial clearance of radioactivity from HDL (control 6.8 vs. TP1 4.1 pools/d) and plasma (7.8 vs. 5.2 pools/d). We conclude that CETP plays a quantitatively important role in HDL CE catabolism in the rabbit, promoting the exchange of TG for CE and the clearance of CE from plasma.

[1]  R. Mahley,et al.  Chylomicron-chylomicron remnant clearance by liver and bone marrow in rabbits. Factors that modify tissue-specific uptake. , 1989, The Journal of biological chemistry.

[2]  A. Tall,et al.  Inhibition of cholesteryl ester transfer protein activity by monoclonal antibody. Effects on cholesteryl ester formation and neutral lipid mass transfer in human plasma. , 1989, The Journal of clinical investigation.

[3]  A. Tall,et al.  Monoclonal antibodies to the Mr 74,000 cholesteryl ester transfer protein neutralize all of the cholesteryl ester and triglyceride transfer activities in human plasma. , 1988, The Journal of biological chemistry.

[4]  H. Mabuchi,et al.  Decreased serum cholesteryl-ester transfer activity in a patient with familial hyper-alpha-lipoproteinemia. , 1988, Clinica chimica acta; international journal of clinical chemistry.

[5]  R. Havel,et al.  Effect of low density lipoprotein receptor deficiency on the metabolism of apolipoprotein B-100 in blood plasma. Kinetic studies in normal and Watanabe heritable hyperlipidemic rabbits. , 1987, The Journal of clinical investigation.

[6]  A. Tall,et al.  Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein. , 1987, The Journal of clinical investigation.

[7]  A. Tall,et al.  Human plasma cholesteryl ester transfer protein enhances the transfer of cholesteryl ester from high density lipoproteins into cultured HepG2 cells. , 1987, The Journal of biological chemistry.

[8]  S. Eisenberg,et al.  In vivo conversion of human HDL3 to HDL2 and apoE-rich HDL1 in the rat: effects of lipid transfer protein. , 1987, Journal of lipid research.

[9]  J. Groener,et al.  A hyperalphalipoproteinaemic family with normal cholesteryl ester transfer/exchange activity. , 1987, The Biochemical journal.

[10]  A. Tall,et al.  Purification and characterization of a human plasma cholesteryl ester transfer protein. , 1987, The Journal of biological chemistry.

[11]  P. Barter,et al.  Effects of sucrose feeding and injection of lipid transfer protein on rat plasma lipoproteins. , 1986, Comparative biochemistry and physiology. B, Comparative biochemistry.

[12]  H. Mabuchi,et al.  Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. , 1985, Atherosclerosis.

[13]  W. Bochenek,et al.  Poloxalene 2930, a hydrophobic surfactant that prevents atherosclerosis, alters composition of rabbit lipoproteins. , 1985, Atherosclerosis.

[14]  S. Eisenberg.  Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters. , 1985, Journal of lipid research.

[15]  P. Barter,et al.  Effects of injecting exogenous lipid transfer protein into rats. , 1985, Biochimica et biophysica acta.

[16]  Y. Marcel,et al.  Comparison of very-low-density lipoproteins isolated from rat liver perfusate, rat serum and human plasma as acceptors for cholesteryl ester transfer. , 1984, Biochimica et biophysica acta.

[17]  S. Eisenberg,et al.  Plasma triglyceride determines structure-composition in low and high density lipoproteins. , 1984, Arteriosclerosis.

[18]  R. Havel,et al.  Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in normal and lipoprotein lipase-deficient humans. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Havel,et al.  Impaired receptor-mediated catabolism of low density lipoproteins in fasted rabbits. , 1984, Journal of lipid research.

[20]  D. B. Zilversmit,et al.  Inter-relationship of lipids transferred by the lipid-transfer protein isolated from human lipoprotein-deficient plasma. , 1983, The Journal of biological chemistry.

[21]  J P Kane,et al.  Cholesterol net transport, esterification, and transfer in human hyperlipidemic plasma. , 1983, The Journal of clinical investigation.

[22]  D. B. Zilversmit,et al.  A plasma inhibitor of triglyceride and cholesteryl ester transfer activities. , 1981, The Journal of biological chemistry.

[23]  Y. Marcel,et al.  Transfer of cholesterol esters between human high density lipoproteins and triglyceride-rich lipoproteins controlled by a plasma protein factor. , 1980, Atherosclerosis.

[24]  J. Avigan,et al.  Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells. , 1978, Journal of lipid research.

[25]  L. Gallo,et al.  Enzymatic assay for cholesterol ester hydrolase activity. , 1978, Journal of lipid research.

[26]  J. Heider,et al.  The picomole determination of free and total cholesterol in cells in culture. , 1978, Journal of lipid research.

[27]  M. Takayama,et al.  A new enzymatic method for determination of serum choline-containing phospholipids. , 1977, Clinica chimica acta; international journal of clinical chemistry.

[28]  D. B. Zilversmit,et al.  Influx of cholesterol into plasma in rabbits with fasting hyperbetalipoproteinemia. , 1974, Journal of lipid research.

[29]  L. Smith,et al.  EFFECT OF VERY LOW-DENSITY LIPOPROTEINS ON LIPID TRANSFER IN INCUBATED SERUM. , 1965, Journal of lipid research.

[30]  A. Nichols,et al.  THE FATE OF CHOLESTERYL ESTERS IN HUMAN SERUM INCUBATED IN VITRO AT 38 DEGREES. , 1964, Biochimica et biophysica acta.

[31]  P. B. Sawin,et al.  MORPHOGENETIC STUDIES OF THE RABBITXIV. Manifestations of regional growth at onset of vertebral ossification , 1955 .

[32]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[33]  H. Hodge,et al.  Distribution of Body Weight in the Organs and Tissues of the Rabbit.∗ , 1941 .

[34]  W. Brown,et al.  ORGAN WEIGHTS OF NORMAL RABBITS , 1925, The Journal of experimental medicine.