Apoprotein E suppresses phytohemagglutinin-activated phospholipid turnover in peripheral blood mononuclear cells.
Plasma lipoproteins with hydrated densities less than 1.063 g/ml, very low density, intermediate density, and low density lipoproteins, suppress mitogen-activated inductive biochemical events in lymphocytes. The ability of these lipoproteins to inhibit phytohemagglutinin (PHA)-enhanced incorporation of 32P into lymphocyte phospholipids correlates directly with the amount of associated apoprotein E (apo-E). Apo-E purified from the very low density lipoproteins of subjects with Types III, IV, and V hyperlipoproteinemia also inhibits PHA-induced 32P-phospholipid formation. With all of the apo-E preparations, 50% suppression occurs at approximately 2-4 microgram/ml and 100% suppression at 4-10 microgram/ml. Moreover, delipidated apo-E is an inhibitory as apo-E complexed with dimyristoyl phosphatidylcholine or with sphingomyelin. Other apoproteins, apo-AI, -AII, -CI, and -CIII, do not inhibit PHA-activated phospholipid turnover, indicating that suppression is due to a specific structural feature of apo-E. Suppression by apo-E is not due to a shift in the optimum concentration of PHA, nor is it the result of competition with PHA for mitogen receptors at the cell surface. These data, taken together with the results of previous studies (Hui, D. Y., and Harmony, J. A. K. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 4764-4768; Hui, D. Y., Harmony, J. A. K. (1980) J. Biol. Chem. 255, 11775-11781), indicate that lipoprotein-associated apo-E serves as a recognition determinant for lymphocyte surface receptors and as a suppressive lipoprotein constituent.
D001053:Apolipoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D001057:Apolipoproteins E; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood*; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood*; D010835:Phytohemagglutinins / Q000494:pharmacology*
D001053:Apolipoproteins; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D010835:Phytohemagglutinins