Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 May;61(5):1298–1308. doi: 10.1172/JCI109047

Identification of a lymphocyte surface receptor for low density lipoprotein inhibitor, an immunoregulatory species of normal human serum low density lipoprotein.

L K Curtiss, T S Edgington
PMCID: PMC372652  PMID: 207735

Abstract

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.

Full text

PDF
1302

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bierman E. L., Stein O., Stein Y. Lipoprotein uptake and metabolism by rat aortic smooth muscle cells in tissue culture. Circ Res. 1974 Jul;35(1):136–150. doi: 10.1161/01.res.35.1.136. [DOI] [PubMed] [Google Scholar]
  2. Brown M. S., Goldstein J. L. Receptor-mediated control of cholesterol metabolism. Science. 1976 Jan 16;191(4223):150–154. doi: 10.1126/science.174194. [DOI] [PubMed] [Google Scholar]
  3. Brown M. S., Goldstein J. L. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell. 1975 Nov;6(3):307–316. doi: 10.1016/0092-8674(75)90182-8. [DOI] [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. Chisari F. V., Edgington T. S. Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein. J Exp Med. 1975 Nov 1;142(5):1092–1107. doi: 10.1084/jem.142.5.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chisari F. V., Gealy W. J., Edgington T. S. Recovery of soluble sheep erythrocyte receptor from the T lymphocyte surface by proteolytic cleavage. J Immunol. 1977 Apr;118(4):1138–1142. [PubMed] [Google Scholar]
  7. Chisari F. V., Gerin J. L., Edgington T. S. Immunochemistry of the hepatitis B virus: 125I HB Ag ligand. J Immunol. 1974 Aug;113(2):543–553. [PubMed] [Google Scholar]
  8. Chisari F. V., Routenberg J. A., Edgington T. S. Mechanisms responsible for defective human T-lymphocyte sheep erythrocyte rosette function associated with hepatitis B virus infections. J Clin Invest. 1976 May;57(5):1227–1238. doi: 10.1172/JCI108391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cuatrecasas P., Hollenberg M. D. Membrane receptors and hormone action. Adv Protein Chem. 1976;30:251–451. doi: 10.1016/s0065-3233(08)60481-7. [DOI] [PubMed] [Google Scholar]
  10. Curtiss L. K., DeHeer D. H., Edgington T. S. In vivo suppression of the primary immune response by a species of low density serum lipoprotein. J Immunol. 1977 Feb;118(2):648–652. [PubMed] [Google Scholar]
  11. Curtiss L. K., Edgington T. S. Effect of LDL-In, a normal immunoregulatory human serum low density lipoprotein, on the interaction of macrophages with lymphocytes proliferating in response to mitogen and allogeneic stimulation. J Immunol. 1977 Jun;118(6):1966–1970. [PubMed] [Google Scholar]
  12. Curtiss L. K., Edgington T. S. Regulatory serum lipoproteins: regulation of lymphocyte stimulation by a species of low density lipoprotein. J Immunol. 1976 May;116(5):1452–1458. [PubMed] [Google Scholar]
  13. Dana S. E., Brown M. S., Goldstein J. L. Specific, saturable, and high affinity binding of 125I-low density lipoprotein to glass beads. Biochem Biophys Res Commun. 1977 Feb 21;74(4):1369–1376. doi: 10.1016/0006-291x(77)90593-9. [DOI] [PubMed] [Google Scholar]
  14. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  15. Goldstein J. L., Brown M. S. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed] [Google Scholar]
  16. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ho Y. K., Brown M. S., Kayden H. J., Goldstein J. L. Binding, internalization, and hydrolysis of low density lipoprotein in long-term lymphoid cell lines from a normal subject and a patient with homozygous familial hypercholesterolemia. J Exp Med. 1976 Aug 1;144(2):444–455. doi: 10.1084/jem.144.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ho Y. K., Brown S., Bilheimer D. W., Goldstein J. L. Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes. J Clin Invest. 1976 Dec;58(6):1465–1474. doi: 10.1172/JCI108603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES