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. 1992 Jul;89(1):1–7. doi: 10.1111/j.1365-2249.1992.tb06868.x

In vivo clearance by the mononuclear phagocyte system in humans: an overview of methods and their interpretation.

C Halma 1, M R Daha 1, L A van Es 1
PMCID: PMC1554409  PMID: 1628416

Abstract

The mononuclear phagocyte system (MPS) is responsible for the elimination of foreign material, effete autologous material and immune complexes. To study the relationship between MPS function and human disease, several test substances have been developed, and used to determine the clearance capacity of the MPS in human subjects in vivo. These test substances and the multitude of factors that influence the elimination of these substances (and complicate the interpretation of the test results) are discussed. Use of these probes has provided important new insights, that may lead to the development of treatment modalities by which MPS function is modified in order to influence disease processes more effectively.

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Selected References

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  1. Arend W. P., Mannik M. Studies on antigen-antibody complexes. II. Quantification of tissue uptake of soluble complexes in normal and complement-depleted rabbits. J Immunol. 1971 Jul;107(1):63–75. [PubMed] [Google Scholar]
  2. Atkinson J. P., Schreiber A. D., Frank M. M. Effects of corticosteroids and splenectomy on the immune clearance and destruction of erythrocytes. J Clin Invest. 1973 Jun;52(6):1509–1517. doi: 10.1172/JCI107325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BENACERRAF B., BIOZZI G., HALPERN B. N., STIFFEL C., MOUTON D. Phagocytosis of heat-denatured human serum albumin labelled with 131I and its use as a means of investigating liver blood flow. Br J Exp Pathol. 1957 Feb;38(1):35–48. [PMC free article] [PubMed] [Google Scholar]
  4. BENACERRAF B., SEBESTYEN M., COOPER N. S. The clearance of antigen antibody complexes from the blood by the reticuloendothelial system. J Immunol. 1959 Feb;82(2):131–137. [PubMed] [Google Scholar]
  5. 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]
  6. BIOZZI G., STIFFEL C., HALPERN B. N., MOUTON D. Lack of action of serum opsonins in phagocytosis of inert particles by cells of reticuloendothelial system. Proc Soc Exp Biol Med. 1963 Apr;112:1017–1020. doi: 10.3181/00379727-112-28239. [DOI] [PubMed] [Google Scholar]
  7. Bender B. S., Bohnsack J. F., Sourlis S. H., Frank M. M., Quinn T. C. Demonstration of defective C3-receptor-mediated clearance by the reticuloendothelial system in patients with acquired immunodeficiency syndrome. J Clin Invest. 1987 Mar;79(3):715–720. doi: 10.1172/JCI112876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bender B. S., Frank M. M., Lawley T. J., Smith W. J., Brickman C. M., Quinn T. C. Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis. 1985 Aug;152(2):409–412. doi: 10.1093/infdis/152.2.409. [DOI] [PubMed] [Google Scholar]
  9. Bigler R. D., Khoo M., Lund-Katz S., Scerbo L., Esfahani M. Identification of low density lipoprotein as a regulator of Fc receptor-mediated phagocytosis. Proc Natl Acad Sci U S A. 1990 Jul;87(13):4981–4985. doi: 10.1073/pnas.87.13.4981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CROME P., MOLLISON P. L. SPLENIC DESTRUCTION OF RH-SENSITIZED, AND OF HEATED RED CELLS. Br J Haematol. 1964 Apr;10:137–154. doi: 10.1111/j.1365-2141.1964.tb00689.x. [DOI] [PubMed] [Google Scholar]
  11. Ceuppens J. L., Baroja M. L., Van Vaeck F., Anderson C. L. Defect in the membrane expression of high affinity 72-kD Fc gamma receptors on phagocytic cells in four healthy subjects. J Clin Invest. 1988 Aug;82(2):571–578. doi: 10.1172/JCI113634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Clarkson S. B., Bussel J. B., Kimberly R. P., Valinsky J. E., Nachman R. L., Unkeless J. C. Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody. N Engl J Med. 1986 May 8;314(19):1236–1239. doi: 10.1056/NEJM198605083141907. [DOI] [PubMed] [Google Scholar]
  13. Clarkson S. B., Kimberly R. P., Valinsky J. E., Witmer M. D., Bussel J. B., Nachman R. L., Unkeless J. C. Blockade of clearance of immune complexes by an anti-Fc gamma receptor monoclonal antibody. J Exp Med. 1986 Aug 1;164(2):474–489. doi: 10.1084/jem.164.2.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Clarkson S. B., Ory P. A. CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes. J Exp Med. 1988 Feb 1;167(2):408–420. doi: 10.1084/jem.167.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cornacoff J. B., Hebert L. A., Smead W. L., VanAman M. E., Birmingham D. J., Waxman F. J. Primate erythrocyte-immune complex-clearing mechanism. J Clin Invest. 1983 Feb;71(2):236–247. doi: 10.1172/JCI110764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Crofton R. W., Diesselhoff-den Dulk M. M., van Furth R. The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state. J Exp Med. 1978 Jul 1;148(1):1–17. doi: 10.1084/jem.148.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Daha M. R., van Es L. A. Fc- and complement receptor-dependent degradation of soluble immune complexes and stable immunoglobulin aggregates by guinea pig monocytes, peritoneal macrophages, and Kupffer cells. J Leukoc Biol. 1984 Nov;36(5):569–579. doi: 10.1002/jlb.36.5.569. [DOI] [PubMed] [Google Scholar]
  18. Elkon K. B., Ferjencik P. P., Walport M. J., Peters A. M., Lewis S. M., Hughes G. R. Evaluation of heat-damaged and IgG-coated red cells for testing reticuloendothelial function. J Immunol Methods. 1982 Dec 17;55(2):253–263. doi: 10.1016/0022-1759(82)90037-0. [DOI] [PubMed] [Google Scholar]
  19. Engelfriet C. P., von dem Borne A. E., Fleer A., van der Meulen F. W., Roos D. In vivo destruction of erythrocytes by complement-binding and non-complement-binding antibodies. Prog Clin Biol Res. 1980;43:213–226. [PubMed] [Google Scholar]
  20. Frank M. M., Hamburger M. I., Lawley T. J., Kimberly R. P., Plotz P. H. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med. 1979 Mar 8;300(10):518–523. doi: 10.1056/NEJM197903083001002. [DOI] [PubMed] [Google Scholar]
  21. Frank M. M., Lawley T. J., Hamburger M. I., Brown E. J. NIH Conference: Immunoglobulin G Fc receptor-mediated clearance in autoimmune diseases. Ann Intern Med. 1983 Feb;98(2):206–218. doi: 10.7326/0003-4819-98-2-218. [DOI] [PubMed] [Google Scholar]
  22. Friedman D., Netti F., Schreiber A. D. Effect of estradiol and steroid analogues on the clearance of immunoglobulin G-coated erythrocytes. J Clin Invest. 1985 Jan;75(1):162–167. doi: 10.1172/JCI111669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gomez F., Chien P., King M., McDermott P., Levinson A. I., Rossman M. D., Schreiber A. D. Monocyte Fc gamma receptor recognition of cell-bound and aggregated IgG. Blood. 1989 Aug 15;74(3):1058–1065. [PubMed] [Google Scholar]
  24. Haakenstad A. O., Mannik M. Saturation of the reticuloendothelial system with soluble immune complexes. J Immunol. 1974 May;112(5):1939–1948. [PubMed] [Google Scholar]
  25. Halma C., Breedveld F. C., Daha M. R., Blok D., Evers-Schouten J. H., Hermans J., Pauwels E. K., van Es L. A. Elimination of soluble 123I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1. Arthritis Rheum. 1991 Apr;34(4):442–452. doi: 10.1002/art.1780340409. [DOI] [PubMed] [Google Scholar]
  26. Hamburger M. I., Lawley T. J., Kimberly R. P., Plotz P. H., Frank M. M. A serial study of splenic reticuloendothelial system Fc receptor functional activity in systemic lupus erythematosus. Arthritis Rheum. 1982 Jan;25(1):48–54. doi: 10.1002/art.1780250108. [DOI] [PubMed] [Google Scholar]
  27. Hebert L. A., Cosio G. The erythrocyte-immune complex-glomerulonephritis connection in man. Kidney Int. 1987 Apr;31(4):877–885. doi: 10.1038/ki.1987.81. [DOI] [PubMed] [Google Scholar]
  28. Hopf U., Meyer zum Büschenfelde K. H., Dierich M. P. Demonstration of binding sites for IgG Fc and the third complement component (C3) on isolated hepatocytes. J Immunol. 1976 Aug;117(2):639–645. [PubMed] [Google Scholar]
  29. Hopf U., Schaefer H. E., Hess G., Meyer Zum Büschenfelde K. H. In vivo uptake of immune complexes by parenchymal and nonparenchymal liver cells in mice. Gastroenterology. 1981 Feb;80(2):250–259. [PubMed] [Google Scholar]
  30. Hosea S. W., Brown E. J., Hamburger M. I., Frank M. M. Opsonic requirements for intravascular clearance after splenectomy. N Engl J Med. 1981 Jan 29;304(5):245–250. doi: 10.1056/NEJM198101293040501. [DOI] [PubMed] [Google Scholar]
  31. Hume D. A., Pavli P., Donahue R. E., Fidler I. J. The effect of human recombinant macrophage colony-stimulating factor (CSF-1) on the murine mononuclear phagocyte system in vivo. J Immunol. 1988 Nov 15;141(10):3405–3409. [PubMed] [Google Scholar]
  32. Jaffe C. J., Vierling J. M., Jones E. A., Lawley T. J., Frank M. M. Receptor specific clearance by the reticuloendothelial system in chronic liver diseases. Demonstration of defective C3b-specific clearance in primary biliary cirrhosis. J Clin Invest. 1978 Nov;62(5):1069–1077. doi: 10.1172/JCI109212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jimenez R. A., Mannik M. Evaluation of aggregated IgG in mice as an Fc receptor specific probe of the hepatic mononuclear phagocyte system. Clin Exp Immunol. 1982 Jul;49(1):200–208. [PMC free article] [PubMed] [Google Scholar]
  34. Kabbash L., Esdaile J., Shenker S., Decary F., Danoff D., Fuks A., Shuster J. Reticuloendothelial system Fc receptor function in systemic lupus erythematosus: effect of decreased sensitization on clearance of autologous erythrocytes. J Rheumatol. 1987 Jun;14(3):487–489. [PubMed] [Google Scholar]
  35. Kelton J. G. Impaired reticuloendothelial function in patients treated with methyldopa. N Engl J Med. 1985 Sep 5;313(10):596–600. doi: 10.1056/NEJM198509053131002. [DOI] [PubMed] [Google Scholar]
  36. Kelton J. G., Singer J., Rodger C., Gauldie J., Horsewood P., Dent P. The concentration of IgG in the serum is a major determinant of Fc-dependent reticuloendothelial function. Blood. 1985 Sep;66(3):490–495. [PubMed] [Google Scholar]
  37. Kijlstra A., Knutson D. W., Daha M. R., van Es L. A. Clearance and glomerular localization of preformed DNP anti-DNP immune complexes. Scand J Immunol. 1979;10(5):421–429. doi: 10.1111/j.1365-3083.1979.tb01371.x. [DOI] [PubMed] [Google Scholar]
  38. Kimberly R. P., Parris T. M., Inman R. D., McDougal J. S. Dynamics of mononuclear phagocyte system Fc receptor function in systemic lupus erythematosus. Relation to disease activity and circulating immune complexes. Clin Exp Immunol. 1983 Feb;51(2):261–268. [PMC free article] [PubMed] [Google Scholar]
  39. Lawley T. J., Hall R. P., Fauci A. S., Katz S. I., Hamburger M. I., Frank M. M. Defective Fc-receptor functions associated with the HLA-B8/DRw3 haplotype: studies in patients with dermatitis herpetiformis and normal subjects. N Engl J Med. 1981 Jan 22;304(4):185–192. doi: 10.1056/NEJM198101223040401. [DOI] [PubMed] [Google Scholar]
  40. Lobatto S., Daha M. R., Breedveld F. C., Pauwels E. K., Evers-Schouten J. H., Voetman A. A., Cats A., Van Es L. A. Abnormal clearance of soluble aggregates of human immunoglobulin G in patients with systemic lupus erythematosus. Clin Exp Immunol. 1988 Apr;72(1):55–59. [PMC free article] [PubMed] [Google Scholar]
  41. Lobatto S., Daha M. R., Voetman A. A., Evers-Schouten J. H., Van Es A. A., Pauwels E. K., Van Es L. A. Clearance of soluble aggregates of human immunoglobulin G in healthy volunteers and chimpanzees. Clin Exp Immunol. 1987 Jul;69(1):133–141. [PMC free article] [PubMed] [Google Scholar]
  42. Lockwood C. M., Worlledge S., Nicholas A., Cotton C., Peters D. K. Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange. N Engl J Med. 1979 Mar 8;300(10):524–530. doi: 10.1056/NEJM197903083001003. [DOI] [PubMed] [Google Scholar]
  43. MOLLISON P. L., CROME P., HUGHES-JONES N. C., ROCHNA E. RATE OF REMOVAL FROM THE CIRCULATION OF RED CELLS SENSITIZED WITH DIFFERENT AMOUNTS OF ANTIBODY. Br J Haematol. 1965 Jul;11:461–470. doi: 10.1111/j.1365-2141.1965.tb06609.x. [DOI] [PubMed] [Google Scholar]
  44. Michael A. F., Fish A. J., Good R. A. Glomerular localization and transport of aggregated proteins in mice. Lab Invest. 1967 Jul;17(1):14–29. [PubMed] [Google Scholar]
  45. Muro H., Shirasawa H., Maeda M., Nakamura S. Fc receptors of liver sinusoidal endothelium in normal rats and humans. A histologic study with soluble immune complexes. Gastroenterology. 1987 Nov;93(5):1078–1085. doi: 10.1016/0016-5085(87)90572-5. [DOI] [PubMed] [Google Scholar]
  46. Parris T. M., Kimberly R. P., Inman R. D., McDougal J. S., Gibofsky A., Christian C. L. Defective Fc receptor-mediated function of the mononuclear phagocyte system in lupus nephritis. Ann Intern Med. 1982 Oct;97(4):526–532. doi: 10.7326/0003-4819-97-4-526. [DOI] [PubMed] [Google Scholar]
  47. Peters A. M., Walport M. J., Elkon K. B., Reavy H. J., Ferjencik P. P., Lavender J. P., Hughes G. R. The comparative blood clearance kinetics of modified radiolabelled erythrocytes. Clin Sci (Lond) 1984 Jan;66(1):55–62. doi: 10.1042/cs0660055. [DOI] [PubMed] [Google Scholar]
  48. Ross G. D. Complement and complement receptors. Curr Opin Immunol. 1989 Oct;2(1):50–62. doi: 10.1016/0952-7915(89)90097-6. [DOI] [PubMed] [Google Scholar]
  49. Rosse W. F. The spleen as a filter. N Engl J Med. 1987 Sep 10;317(11):704–706. doi: 10.1056/NEJM198709103171110. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Salmon J. E., Kapur S., Meryhew N. L., Runquist O. A., Kimberly R. P. High-dose, pulse intravenous methylprednisolone enhances Fc gamma receptor-mediated mononuclear phagocyte function in systemic lupus erythematosus. Arthritis Rheum. 1989 Jun;32(6):717–725. doi: 10.1002/anr.1780320609. [DOI] [PubMed] [Google Scholar]
  52. Schifferli J. A., Ng Y. C., Estreicher J., Walport M. J. The clearance of tetanus toxoid/anti-tetanus toxoid immune complexes from the circulation of humans. Complement- and erythrocyte complement receptor 1-dependent mechanisms. J Immunol. 1988 Feb 1;140(3):899–904. [PubMed] [Google Scholar]
  53. Schifferli J. A., Ng Y. C., Paccaud J. P., Walport M. J. The role of hypocomplementaemia and low erythrocyte complement receptor type 1 numbers in determining abnormal immune complex clearance in humans. Clin Exp Immunol. 1989 Mar;75(3):329–335. [PMC free article] [PubMed] [Google Scholar]
  54. Schned E. S., Inman R. D., Parris T. M., Kimberly R. P., Redecha P. B., Christian C. L. Serial circulating immune complexes and mononuclear phagocyte system function in infective endocarditis. J Lab Clin Med. 1983 Dec;102(6):947–959. [PubMed] [Google Scholar]
  55. Schreiber A. D., Nettl F. M., Sanders M. C., King M., Szabolcs P., Friedman D., Gomez F. Effect of endogenous and synthetic sex steroids on the clearance of antibody-coated cells. J Immunol. 1988 Nov 1;141(9):2959–2966. [PubMed] [Google Scholar]
  56. Taylor R. P., Sutherland W. M., Reist C. J., Webb D. J., Wright E. L., Labuguen R. H. Use of heteropolymeric monoclonal antibodies to attach antigens to the C3b receptor of human erythrocytes: a potential therapeutic treatment. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3305–3309. doi: 10.1073/pnas.88.8.3305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Thompson J., van Furth R. The effect of glucocorticosteroids on the kinetics of mononuclear phagocytes. J Exp Med. 1970 Mar 1;131(3):429–442. doi: 10.1084/jem.131.3.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Thornburg R. W., Day J. F., Baynes J. W., Thorpe S. R. Carbohydrate-mediated clearance of immune complexes from the circulation. A role for galactose residues in the hepatic uptake of IgG-antigen complexes. J Biol Chem. 1980 Jul 25;255(14):6820–6825. [PubMed] [Google Scholar]
  59. Unkeless J. C., Scigliano E., Freedman V. H. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. doi: 10.1146/annurev.iy.06.040188.001343. [DOI] [PubMed] [Google Scholar]
  60. Veerhuis R., Krol M. C., van Es L. A., Daha M. R. Difference in clearance kinetics of particulate immune complexes and soluble aggregates of IgG in vivo. Clin Immunol Immunopathol. 1986 Dec;41(3):379–391. doi: 10.1016/0090-1229(86)90008-5. [DOI] [PubMed] [Google Scholar]
  61. 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]
  62. Walport M. J., Peters A. M., Elkon K. B., Pusey C. D., Lavender J. P., Hughes G. R. The splenic extraction ratio of antibody-coated erythrocytes and its response to plasma exchange and pulse methylprednisolone. Clin Exp Immunol. 1985 Jun;60(3):465–473. [PMC free article] [PubMed] [Google Scholar]
  63. Waxman F. J., Hebert L. A., Cosio F. G., Smead W. L., VanAman M. E., Taguiam J. M., Birmingham D. J. Differential binding of immunoglobulin A and immunoglobulin G1 immune complexes to primate erythrocytes in vivo. Immunoglobulin A immune complexes bind less well to erythrocytes and are preferentially deposited in glomeruli. J Clin Invest. 1986 Jan;77(1):82–89. doi: 10.1172/JCI112306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Williams B. D., O'Sullivan M. M., Ratanachaiyavong S. Reticuloendothelial Fc function in normal individuals and its relationship to the HLA antigen DR3. Clin Exp Immunol. 1985 Jun;60(3):532–538. [PMC free article] [PubMed] [Google Scholar]
  65. van Aken W. G., Goote T. M., Vreeken J. Platelet aggregation: an intermediary mechanism in carbon clearance. Scand J Haematol. 1968;5(5):333–338. doi: 10.1111/j.1600-0609.1968.tb01757.x. [DOI] [PubMed] [Google Scholar]

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