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. 1975 Nov 1;142(5):1092–1107. doi: 10.1084/jem.142.5.1092

Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein

PMCID: PMC2189976  PMID: 172585

Abstract

Rosette inhibitory factor, RIF, previously described in serum from patients with hepatitis B virus infection, has been isolated and identified as a minor species of beta-lipoprotein of the low-density (LDL) class. It is unrelated to hepatitis B virus proteins or particles. Although discrete by reference to charge and density (1.050 +/- 0.004 g/cm3), RIF appears to be a complex macromolecular structure containing apolipoproteins A, B, and C. Greater than 400% recovery is achieved upon 300,000-fold purification from RIF+ sera suggesting activation of a precursor form that is not present in normal serum. RIF inhibits E rosette function of T lymphocytes in vitro with a lag period of approximately 4 h and maximal effect at 24 h consistent with a metabolically-induced event. RIF is functionally active at concentrations of 1 X 10(-12) M or greater, rapidly binds to lymphocytes, and has a functionally effective half-life of approximately 1.5 h. Approximately 2,900 receptors for RIF appear to be present per cell and a high mutual affinity is apparent (k approximately to 9 X 10(10) liters/mol). RIF has no detectable effect on mitogen (PHA) responsiveness of lymphocytes, but inhibits the capacity of lymphocytes to respond to histoincompatible cells in vitro at concentrations greater than 10(-8) M. Equivalent RIF- lipoprotein fractions from normal serum are equally inhibitory in the mixed lymphocyte reaction suggesting that this effect is not directly attributable to RIF activity. These data indicate that RIF is a unique and functionally specific species of LDL that represents either an association complex of lipoproteins or a hybrid molecule of unusual composition. The association of this factor with viral-induced hepatocellular injury underscores the need to elucidate its structure and function in greater detail.

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Selected References

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

  1. Alaupovic P., Lee D. M., McConathy W. J. Studies on the composition and structure of plasma lipoproteins. Distribution of lipoprotein families in major density classes of normal human plasma lipoproteins. Biochim Biophys Acta. 1972 Apr 18;260(4):689–707. [PubMed] [Google Scholar]
  2. Bentwich Z., Douglas S. D., Siegal F. P., Kunkel H. G. Human lymphocyte-sheep erythrocyte rosette formation: some characteristics of the interaction. Clin Immunol Immunopathol. 1973 Jul;1(4):511–522. doi: 10.1016/0090-1229(73)90007-x. [DOI] [PubMed] [Google Scholar]
  3. Chase P. S. The effects of human serum fractions on phytohemagglutinin- and concanavalin A-stimulated human lymphocyte cultures. Cell Immunol. 1972 Dec;5(4):544–554. doi: 10.1016/0008-8749(72)90104-9. [DOI] [PubMed] [Google Scholar]
  4. Chisari F. V., Edgington T. S. Human T lymphocyte "E" rosette function. I. A process modulated by intracellular cyclic AMP. J Exp Med. 1974 Oct 1;140(4):1122–1126. doi: 10.1084/jem.140.4.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chisari F. V., Northrup R. S., Chen L. C. The modulating effect of cholera enterotoxin on the immune response. J Immunol. 1974 Sep;113(3):729–739. [PubMed] [Google Scholar]
  6. Galant S. P., Remo R. A. Beta-adrenergic inhibition of human T lymphocyte rosettes. J Immunol. 1975 Jan;114(1 Pt 2):512–513. [PubMed] [Google Scholar]
  7. Gatti R. A., Svedmyr A. J., Wigzell H. Characterization of a serum inhibitor of MLC reactions. II. Molecular structure and dissociation of inhibition against responder and stimulator function. Cell Immunol. 1974 Mar 30;11(1-3):466–477. doi: 10.1016/0008-8749(74)90044-6. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Hartzman R. J., Bach M. L., Bach F. H., Thurman G. B., Sell K. W. Precipitation of radioactively labeled samples: a semi-automatic multiple-sample processor. Cell Immunol. 1972 Jun;4(2):182–186. doi: 10.1016/0008-8749(72)90018-4. [DOI] [PubMed] [Google Scholar]
  10. Hatch F. T. Practical methods for plasma lipoprotein analysis. Adv Lipid Res. 1968;6:1–68. [PubMed] [Google Scholar]
  11. Henney C. S., Bourne H. R., Lichtenstein L. M. The role of cyclic 3',5' adenosine monophosphate in the specific cytolytic activity of lymphocytes. J Immunol. 1972 Jun;108(6):1526–1534. [PubMed] [Google Scholar]
  12. Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Lee D. M., Alaupovic P. Physiocochemical properties of low-density lipoproteins of normal human plasma. Evidence for the occurrence of lipoprotein B in associated and free forms. Biochem J. 1974 Feb;137(2):155–167. doi: 10.1042/bj1370155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ling C. M., Overby L. R. Prevalence of hepatitis B virus antigen as revealed by direct radioimmune assay with 125 I-antibody. J Immunol. 1972 Oct;109(4):834–841. [PubMed] [Google Scholar]
  16. Margolis S. Separation and size determination of human serum lipoproteins by agarose gel filtration. J Lipid Res. 1967 Sep;8(5):501–507. [PubMed] [Google Scholar]
  17. Menzoian J. O., Glasgow A. H., Nimberg R. D., Cooperband S. R., Schmid K., Saporoschetz I., Mannick J. A. Regulation of T lymphocyte function by immunoregulatory alphaglobulin (IRA). J Immunol. 1974 Jul;113(1):266–273. [PubMed] [Google Scholar]
  18. Messner R. P., Lindström F. D., Williams R. C., Jr Peripheral blood lymphocyte cell surface markers during the course of systemic lupus erythematosus. J Clin Invest. 1973 Dec;52(12):3046–3056. doi: 10.1172/JCI107503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mortensen R. F., Osmand A. P., Gewurz H. Effects on C-reactive protein on the lymphoid system. I. Binding to thymus-dependent lymphocytes and alteration of their functions. J Exp Med. 1975 Apr 1;141(4):821–839. [PMC free article] [PubMed] [Google Scholar]
  20. Schumacher K., Maerker-Alzer G., Wehmer U. A lymphocyte-inhibiting factor isolated from normal human liver. Nature. 1974 Oct 18;251(5476):655–656. doi: 10.1038/251655a0. [DOI] [PubMed] [Google Scholar]
  21. Seidel D., Alaupovic P., Furman R. H. A lipoprotein characterizing obstructive jaundice. I. Method for quantitative separation and identification of lipoproteins in jaundiced subjects. J Clin Invest. 1969 Jul;48(7):1211–1223. doi: 10.1172/JCI106085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Skipski V. P., Barclay M., Barclay R. K., Fetzer V. A., Good J. J., Archibald F. M. Lipid composition of human serum lipoproteins. Biochem J. 1967 Aug;104(2):340–352. doi: 10.1042/bj1040340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith J. W., Steiner A. L., Parker C. W. Human lymphocytic metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin. J Clin Invest. 1971 Feb;50(2):442–448. doi: 10.1172/JCI106511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thurman G. B., Strong D. M., Ahmed A., Green S. S., Sell K. W., Hartzman R. J., Bach F. H. Human mixed lymphocyte cultures. Evaluation of a microculture technique utilizing the Multiple Automated Sample Harvester (MASH). Clin Exp Immunol. 1973 Oct;15(2):289–302. [PMC free article] [PubMed] [Google Scholar]
  25. Wybran J., Fudenberg H. H. Thymus-derived rosette-forming cells in various human disease states: cancer, lymphoma, bacterial and viral infections, and other diseases. J Clin Invest. 1973 May;52(5):1026–1032. doi: 10.1172/JCI107267. [DOI] [PMC free article] [PubMed] [Google Scholar]

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