Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 Nov;62(5):1069–1077. doi: 10.1172/JCI109212

Receptor Specific Clearance by the Reticuloendothelial System in Chronic Liver Diseases

DEMONSTRATION OF DEFECTIVE C3b-SPECIFIC CLEARANCE IN PRIMARY BILIARY CIRRHOSIS

Charles J Jaffe 1,2,3,4, John M Vierling 1,2,3,4, E Anthony Jones 1,2,3,4, Thomas J Lawley 1,2,3,4, Michael M Frank 1,2,3,4
PMCID: PMC371867  PMID: 711852

Abstract

An approach to the assessment of reticuloendothelial function that quantitates clearance specifically mediated by membrane receptors for C3b and immunoglobulin (Ig)G has been applied in man. Clearance of isologous erythrocytes coated with IgM or C3b or coated with IgG were examined in patients with primary biliary cirrhosis (PBC), chronic hepatitis, or alcoholic cirrhosis and normal control subjects and compared with the clearance of aggregated human serum albumin. Clearance of these three types of particles varied independently. None of the patients studied had a defect in the clearance of aggregated albumin. No patient with PBC (0:6) had delayed clearance of IgG-coated erythrocytes; one of six patients with chronic hepatitis had delayed clearance of these cells. Indeed, four of six with PBC had increased rates of IgG-mediated clearance. In contrast, six out of six patients with PBC had an unequivocal defect in clearance mediated by C3b receptors. The patients with PBC varied widely in terms of duration of symptoms, degree of cholestasis, and histologic stage of disease. No defect of C3b-mediated erythrocyte clearance was found in the patients with chronic hepatitis or alcoholic cirrhosis. Furthermore, a patient with severe cholestasis secondary to large duct biliary obstruction exhibited normal C3b-mediated clearance. The defect in C3b-mediated clearance in PBC did not correlate with serum levels of individual complement components or inhibitors or with the presence of circulating immune complexes as measured by the Clq precipitation assay. Thus, measurements of receptor specific clearance, but not clearance of aggregated proteins, have revealed a highly specific defect in reticuloendothelial function in PBC.

Full text

PDF
1071

Selected References

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

  1. Atkinson J. P., Frank M. M. Studies on the in vivo effects of antibody. Interaction of IgM antibody and complement in the immune clearance and destruction of erythrocytes in man. J Clin Invest. 1974 Aug;54(2):339–348. doi: 10.1172/JCI107769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atkinson J. P., Frank M. M. The effect of Bacillus Calmette-Guerin-induced macrophage activation on the in vivo clearance of sensitized erythrocytes. J Clin Invest. 1974 Jun;53(6):1742–1749. doi: 10.1172/JCI107726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BIOZZI G., BENACERRAF B., HALPERN B. N., STIFFEL C., HILLEMAND B. Exploration of the phagocytic function of the reticuloendothelial system with heat denatured human serum albumin labeled with I131 and application to the measurement of liver blood flow, in normal man and in some pathologic conditions. J Lab Clin Med. 1958 Feb;51(2):230–239. [PubMed] [Google Scholar]
  4. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borsos T., Colten H. R., Spalter J. S., Rogentine N., Rapp H. J. The C'la fixation and transfer test: examples of its applicability to the detection and enumeration of antigens and antibodies at cell surfaces. J Immunol. 1968 Sep;101(3):392–398. [PubMed] [Google Scholar]
  6. Boyer J. L. Chronic hepatitis--a perspective on classification and determinants of prognosis. Gastroenterology. 1976 Jun;70(6):1161–1171. [PubMed] [Google Scholar]
  7. Briner W. H. Preparation of 125I-labeled microaggregated human serum albumin for use in studies of reticuloendothelial function in man. J Nucl Med. 1968 Sep;9(9):482–485. [PubMed] [Google Scholar]
  8. DOBSON E. L., WARNER G. F., FINNEY C. R., JOHNSTON M. E. The measurement of liver circulation by means of the colloid disappearance rate. I. Liver blood flow in normal young men. Circulation. 1953 May;7(5):690–695. doi: 10.1161/01.cir.7.5.690. [DOI] [PubMed] [Google Scholar]
  9. Elias E., Potter B. J., Thomas H. C., Sherlock S. Proceedings: C3 metabolism in HBsAg positive and negative chronic active liver disease (CALD). Gut. 1976 May;17(5):389–389. [PubMed] [Google Scholar]
  10. Gaither T. A., Alling D. W., Frank M. M. A new one-step method for the functional assay of the fourth component (C4) of human and guinea pig complement. J Immunol. 1974 Aug;113(2):574–583. [PubMed] [Google Scholar]
  11. Hoofnagle J. H., Gerety R. J., Barker L. F. Antibody to hepatitis-B-virus core in man. Lancet. 1973 Oct 20;2(7834):869–873. doi: 10.1016/s0140-6736(73)92004-7. [DOI] [PubMed] [Google Scholar]
  12. Jaffe C. J., Atkinson J. P., Frank M. M. The role of complement in the clearance of cold agglutinin-sensitized erythrocytes in man. J Clin Invest. 1976 Oct;58(4):942–949. doi: 10.1172/JCI108547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Martin J. F., Mikulecky M., Blaschike T. F., Waggoner J. G., Vergalla J., Berk P. D. Differences between the plasma indocyanine green disappearance rates of normal men and women. Proc Soc Exp Biol Med. 1975 Dec;150(3):612–617. doi: 10.3181/00379727-150-39090. [DOI] [PubMed] [Google Scholar]
  14. NIH conference. Pathophysiology of immune hemolytic anemia. Ann Intern Med. 1977 Aug;87(2):210–222. doi: 10.7326/0003-4819-87-2-210. [DOI] [PubMed] [Google Scholar]
  15. Plotz P. H. Autoimmunity in hepatitis. Med Clin North Am. 1975 Jul;59(4):869–876. doi: 10.1016/s0025-7125(16)31985-x. [DOI] [PubMed] [Google Scholar]
  16. Potter B. J., Elias E., Jones E. A. Hypercatabolism of the third component of complement in patients with primary biliary cirrhosis. J Lab Clin Med. 1976 Sep;88(3):427–439. [PubMed] [Google Scholar]
  17. Potter B. J., Trueman A. M., Jones E. A. Serum complement in chronic liver disease. Gut. 1973 Jun;14(6):451–456. doi: 10.1136/gut.14.6.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reed W. D., Eddleston A. L., Williams R. Immunopathology of viral hepatitis in man. Prog Med Virol. 1974;17(0):38–76. [PubMed] [Google Scholar]
  19. Reynolds H. Y., Atkinson J. P., Newball H. H., Frank M. M. Receptors for immunoglobulin and complement on human alveolar macrophages. J Immunol. 1975 Jun;114(6):1813–1819. [PubMed] [Google Scholar]
  20. Salky N. K., Mills D., Di Luzio N. R. Activity of the reticuloendothelial system in diseases of altered immunity. J Lab Clin Med. 1965 Dec;66(6):952–960. [PubMed] [Google Scholar]
  21. Schaffner F. Primary biliary cirrhosis. Clin Gastroenterol. 1975 May;4(2):351–366. [PubMed] [Google Scholar]
  22. Sheagren J. N., Block J. B., Wolff S. M. Reticuloendothelial system phagocytic function in patients with Hodgkin's disease. J Clin Invest. 1967 May;46(5):855–862. doi: 10.1172/JCI105585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith M. G., Eddleston A. L., Williams R. Immunological factors in the evolution of active chronic hepatitis and other autoimmune liver diseases. Clin Gastroenterol. 1975 May;4(2):297–313. [PubMed] [Google Scholar]
  24. Teisberg P., Gjone E. Circulating conversion products of C3 in liver disease. Evidence for in vivo activation of the complement system. Clin Exp Immunol. 1973 Aug;14(4):509–514. [PMC free article] [PubMed] [Google Scholar]
  25. Thomas H. C., De Villiers D., Potter B., Hodgson H., Jain S., Jewell D. P., Sherlock S. Immune complexes in acute and chronic liver disease. Clin Exp Immunol. 1978 Feb;31(2):150–157. [PMC free article] [PubMed] [Google Scholar]
  26. WAGNER H. N., Jr, IIO M., HORNICK R. B. Studies of the reticuloendothelial system (RES). II. Changes in the phagocytic capacity of the RES in patients with certain infections. J Clin Invest. 1963 Mar;42:427–434. doi: 10.1172/JCI104730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wands J. R., Dienstag J. L., Bhan A. K., Feller E. R., Isselbacher K. J. Circulating immune complexes and complement activation in primary biliary cirrhosis. N Engl J Med. 1978 Feb 2;298(5):233–237. doi: 10.1056/NEJM197802022980502. [DOI] [PubMed] [Google Scholar]
  28. Yonemasu K., Stroud R. M. Clq: rapid purification method for preparation of monospecific antisera and for biochemical studies. J Immunol. 1971 Feb;106(2):304–313. [PubMed] [Google Scholar]

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

RESOURCES