Identification of a lymphocyte surface receptor for low density lipoprotein inhibitor, an immunoregulatory species of normal human serum low density lipoprotein.
The present study demonstrates the existence on human peripheral blood lymphocytes of a saturable cell surface receptor for low density lipoprotein inhibitor (LDL-In), a subset of normal human serum low density lipoprotein (LDL) that has been previously demonstrated to suppress selected lymphocyte functions in vivo and in vitro. The binding of radioiodinated LDL-In of demonstrable biological activity occurs rapidly and is quantitatively augmented by prior cultivation of the lymphocytes in lipoprotein-depleted serum, suggesting regulation of receptor density by lipoproteins in vivo. Binding is temperature dependent, facilitated by calcium ions, saturable at 4 degrees C within 40-60 min, and blocked by prior exposure to unlabeled LDL-In. The lymphocyte receptor is trypsin sensitive and regenerates in vitro with a t1/2 of 3.6 h. LDL-In receptors are calculated to have a maximum density of 4,860 +/- 460 per cell if uniformly distributed on all lymphocyte subsets. These receptors have an estimated average association constant of 1.47 X 10(7) liters/mol. When considered in context of the estimated concentration of LDL-In in blood, the receptors should be partially occupied in vivo by endogenous plasma LDL-In. Prior site occupancy inhibition experiments designed to analyze the specificity of LDL-In binding demonstrate that (a) LDL-In is 13.7-fold more effective than whole LDL in blocking the subsequent binding of 125I-LDL-In to cells; and that (b) LDL is 11-fold more effective than LDL-In in blocking the binding of 125I-LKL. This is consistent with the degree of contamination of each lipoprotein with the other lipoprotein. An independent identity of the LDL-In receptor is also supported by observations that in contrast to the previously described LDL receptor, synthesis and expression of the LDL-In receptor on lymphocytes are not suppressed by cultivation of the cells in the presence of 25-hydroxycholesterol and cholesterol. These findings suggest the existence of a previously undescribed and discrete receptor on lymphocytes for LDL-In, and that the modulation of lymphocyte function by LDL-In may be mediated by a specific cell surface receptor pathway.
D002784:Cholesterol; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D012397:Rosette Formation
D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011955:Receptors, Drug; D002784:Cholesterol