Inhibition of Ca2+ accumulation in mitogen-activated lymphocytes: role of membrane-bound plasma lipoproteins.
Low density lipoproteins (LDL) in which apoB is the only protein constituent inhibit lymphocyte activation induced by the mitogen phytohemagglutinin. LDL suppress primary induction events, most notably enhanced Ca2+ accumulation, which occur as a result of mitogen-triggered alterations of the lymphocyte plasma membrane. Receptors in the lymphocyte membrane--designated "immunoregulatory receptors"--recognize and bind apoB-LDL. Under conditions of receptor saturation, about 22,500 +/- 4500 LDL particles are bound to the lymphocyte surface at 4 and 37 degrees C. The dissociation constant, Kd, is 1.76 X 10(-7) M and is also independent of temperature. Suppression of phytohemagglutinin-induced 45Ca2+ accumulation by LDL is a receptor-dependent process: inhibition is contingent on attachment of LDL to the immunoregulatory receptors. This conclusion is supported by three lines of evidence. First, heparin restores the susceptibility of the lymphocytes to mitogenic challenge by displacing membrane-bound LDL. Second, the immnoregulatory potency of LDL correlates directly with the amount of LDL bound at the cell surface. Third, LDL-Sepharose complexes, which cannot be internalized by the cells, are as immunosuppressive as soluble LDL. This demonstrates that membrane-bound plasma lipoproteins influence the behavior of intact cells.
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D008077:Lipoproteins, LDL; D010835:Phytohemagglutinins; D002784:Cholesterol; D002118:Calcium