Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1995 Feb;84(2):207–212.

IgA and IgG immune complexes increase human macrophage C3 biosynthesis.

J Laufer 1, H Boichis 1, N Farzam 1, J H Passwell 1
PMCID: PMC1415113  PMID: 7750996

Abstract

We have studied the effect of IgA- and IgG-containing immune complexes on the production of complement proteins C3, factor B and C2 by human monocyte-derived macrophages, using biosynthetic labelling, immunoprecipitation, sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE) and autoradiography. There was a consistent increase in C3 production and secretion with both IgA and IgG immune complexes. This increase appeared after a 24-hr incubation period of the macrophages in the presence of immune complexes. No change in the biosynthesis of factor B and C2 proteins was observed in these experiments. Concomitant with the enhanced C3 biosynthesis, the immune complexes caused an increase in macrophage tumour necrosis factor (TNF) production; 310 + 24 U/ml/5 x 10(5) cells and 430 + 51 U/ml/5 x 10(5) cells for IgA and IgG immune complexes, respectively, versus 12 + 8 U/ml/5 x 10(5) cells in the control cells. The presence of prednisolone (2 x 10(-5) M) or dexamethasone (1 x 10(-7) M) inhibited the immune complex-induced TNF production, but had no effect on C3-increased synthesis, suggesting that the effect of immune complexes was not mediated by endogenous TNF production. These findings may be relevant to the local inflammatory response in IgA immune complex-mediated diseases, including IgA nephropathy.

Full text

PDF
207

Images in this article

209Figure 1
on p.209
209Figure 2
on p.209
209Figure 3
on p.209
210Figure 4
on p.210
210Figure 5
on p.210
210Figure 7
on p.210

Selected References

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

  1. Albrechtsen M., Yeaman G. R., Kerr M. A. Characterization of the IgA receptor from human polymorphonuclear leucocytes. Immunology. 1988 Jun;64(2):201–205. [PMC free article] [PubMed] [Google Scholar]
  2. Alpert S. E., Auerbach H. S., Cole F. S., Colten H. R. Macrophage maturation: differences in complement secretion by marrow, monocyte, and tissue macrophages detected with an improved hemolytic plaque assay. J Immunol. 1983 Jan;130(1):102–107. [PubMed] [Google Scholar]
  3. Atkins R. C., Glasgow E. F., Holdsworth S. R., Thomson N. M., Hancock W. W. Tissue culture of isolated glomeruli from patients with glomerulonephritis. Kidney Int. 1980 Apr;17(4):515–527. doi: 10.1038/ki.1980.60. [DOI] [PubMed] [Google Scholar]
  4. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  5. Boyce N. W., Holdsworth S. R., Thomson N. M., Atkins R. C. Clinicopathological associations in mesangial IgA nephropathy. Am J Nephrol. 1986;6(4):246–252. doi: 10.1159/000167171. [DOI] [PubMed] [Google Scholar]
  6. Circolo A., Pierce G. F., Katz Y., Strunk R. C. Antiinflammatory effects of polypeptide growth factors. Platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor inhibit the cytokine-induced expression of the alternative complement pathway activator factor B in human fibroblasts. J Biol Chem. 1990 Mar 25;265(9):5066–5071. [PubMed] [Google Scholar]
  7. Cole F. S., Auerbach H. S., Goldberger G., Colten H. R. Tissue-specific pretranslational regulation of complement production in human mononuclear phagocytes. J Immunol. 1985 Apr;134(4):2610–2616. [PubMed] [Google Scholar]
  8. Colten H. R. Molecular genetics of the major histocompatibility linked complement genes. Springer Semin Immunopathol. 1983;6(2-3):149–158. doi: 10.1007/BF00205870. [DOI] [PubMed] [Google Scholar]
  9. Czerkinsky C., Koopman W. J., Jackson S., Collins J. E., Crago S. S., Schrohenloher R. E., Julian B. A., Galla J. H., Mestecky J. Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies. J Clin Invest. 1986 Jun;77(6):1931–1938. doi: 10.1172/JCI112522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davin J. C., Foidart J. B., Mahieu P. R. Relation between biological IgA abnormalities and mesangial IgA deposits in isolated hematuria in childhood. Clin Nephrol. 1987 Aug;28(2):73–80. [PubMed] [Google Scholar]
  11. Debets J. M., Ruers T. J., van der Linden M. P., van der Linden C. J., Buurman W. A. Inhibitory effect of corticosteroids on the secretion of tumour necrosis factor (TNF) by monocytes is dependent on the stimulus inducing TNF synthesis. Clin Exp Immunol. 1989 Nov;78(2):224–229. [PMC free article] [PubMed] [Google Scholar]
  12. Debets J. M., Van der Linden C. J., Dieteren I. E., Leeuwenberg J. F., Buurman W. A. Fc-receptor cross-linking induces rapid secretion of tumor necrosis factor (cachectin) by human peripheral blood monocytes. J Immunol. 1988 Aug 15;141(4):1197–1201. [PubMed] [Google Scholar]
  13. Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
  14. Emancipator S. N. Immunoregulatory factors in the pathogenesis of IgA nephropathy. Kidney Int. 1990 Dec;38(6):1216–1229. doi: 10.1038/ki.1990.337. [DOI] [PubMed] [Google Scholar]
  15. Emancipator S. N., Lamm M. E. IgA nephropathy: pathogenesis of the most common form of glomerulonephritis. Lab Invest. 1989 Feb;60(2):168–183. [PubMed] [Google Scholar]
  16. Feehally J., Beattie T. J., Brenchley P. E., Coupes B. M., Mallick N. P., Postlethwaite R. J. Sequential study of the IgA system in relapsing IgA nephropathy. Kidney Int. 1986 Dec;30(6):924–931. doi: 10.1038/ki.1986.274. [DOI] [PubMed] [Google Scholar]
  17. Holdsworth S. R., Neale T. J., Wilson C. B. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an antimacrophage serum. J Clin Invest. 1981 Sep;68(3):686–698. doi: 10.1172/JCI110304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnson K. J., Wilson B. S., Till G. O., Ward P. A. Acute lung injury in rat caused by immunoglobulin A immune complexes. J Clin Invest. 1984 Aug;74(2):358–369. doi: 10.1172/JCI111431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katz Y., Strunk R. C. IL-1 and tumor necrosis factor. Similarities and differences in stimulation of expression of alternative pathway of complement and IFN-beta 2/IL-6 genes in human fibroblasts. J Immunol. 1989 Jun 1;142(11):3862–3867. [PubMed] [Google Scholar]
  20. Kauffmann R. H., Herrmann W. A., Meÿer C. J., Daha M. R., Van Es L. A. Circulating IgA-immune complexes in Henoch-Schönlein purpura. A longitudinal study of their relationship to disease activity and vascular deposition of IgA. Am J Med. 1980 Dec;69(6):859–866. doi: 10.1016/s0002-9343(80)80011-8. [DOI] [PubMed] [Google Scholar]
  21. Kern J. A., Lamb R. J., Reed J. C., Daniele R. P., Nowell P. C. Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. J Clin Invest. 1988 Jan;81(1):237–244. doi: 10.1172/JCI113301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kimura M., Nagase M., Hishida A., Honda N. Intramesangial passage of mononuclear phagocytes in murine lupus glomerulonephritis. Am J Pathol. 1987 Apr;127(1):149–156. [PMC free article] [PubMed] [Google Scholar]
  23. Li H. L., Hancock W. W., Hooke D. H., Dowling J. P., Atkins R. C. Mononuclear cell activation and decreased renal function in IgA nephropathy with crescents. Kidney Int. 1990 Jun;37(6):1552–1556. doi: 10.1038/ki.1990.148. [DOI] [PubMed] [Google Scholar]
  24. Maliszewski C. R., March C. J., Schoenborn M. A., Gimpel S., Shen L. Expression cloning of a human Fc receptor for IgA. J Exp Med. 1990 Dec 1;172(6):1665–1672. doi: 10.1084/jem.172.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mestecky J., McGhee J. R. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol. 1987;40:153–245. doi: 10.1016/s0065-2776(08)60240-0. [DOI] [PubMed] [Google Scholar]
  26. Monteiro R. C., Kubagawa H., Cooper M. D. Cellular distribution, regulation, and biochemical nature of an Fc alpha receptor in humans. J Exp Med. 1990 Mar 1;171(3):597–613. doi: 10.1084/jem.171.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Padeh S., Jaffe C. L., Passwell J. H. Activation of human monocytes via their sIgA receptors. Immunology. 1991 Feb;72(2):188–193. [PMC free article] [PubMed] [Google Scholar]
  28. Passwell J. H., Dayer J. M., Gass K., Edelson P. J. Regulation by Fc fragments of the secretion of collagenase, PGE2, and lysozyme by mouse peritoneal macrophages. J Immunol. 1980 Aug;125(2):910–913. [PubMed] [Google Scholar]
  29. Pfaffenbach G., Lamm M. E., Gigli I. Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes. J Exp Med. 1982 Jan 1;155(1):231–247. doi: 10.1084/jem.155.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Polat G. L., Laufer J., Fabian I., Passwell J. H. Cross-linking of monocyte plasma membrane Fc alpha, Fc gamma or mannose receptors induces TNF production. Immunology. 1993 Oct;80(2):287–292. [PMC free article] [PubMed] [Google Scholar]
  31. Reid K. B., Porter R. R. The proteolytic activation systems of complement. Annu Rev Biochem. 1981;50:433–464. doi: 10.1146/annurev.bi.50.070181.002245. [DOI] [PubMed] [Google Scholar]
  32. Robinson G., Volovitz B., Passwell J. H. Identification of a secretory IgA receptor on breast-milk macrophages: evidence for specific activation via these receptors. Pediatr Res. 1991 May;29(5):429–434. doi: 10.1203/00006450-199105010-00004. [DOI] [PubMed] [Google Scholar]
  33. Ruff M. R., Gifford G. E. Rabbit tumor necrosis factor: mechanism of action. Infect Immun. 1981 Jan;31(1):380–385. doi: 10.1128/iai.31.1.380-385.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Strunk R. C., Cole F. S., Perlmutter D. H., Colten H. R. gamma-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes. J Biol Chem. 1985 Dec 5;260(28):15280–15285. [PubMed] [Google Scholar]
  35. Strunk R. C., Whitehead A. S., Cole F. S. Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide. J Clin Invest. 1985 Sep;76(3):985–990. doi: 10.1172/JCI112099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Valentijn R. M., Radl J., Haaijman J. J., Vermeer B. J., Weening J. J., Kauffmann R. H., Daha M. R., van Es L. A. Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy. Kidney Int. 1984 Nov;26(5):760–766. doi: 10.1038/ki.1984.213. [DOI] [PubMed] [Google Scholar]
  37. Vissers M. C., Fantone J. C., Wiggins R., Kunkel S. L. Glomerular basement membrane-containing immune complexes stimulate tumor necrosis factor and interleukin-1 production by human monocytes. Am J Pathol. 1989 Jan;134(1):1–6. [PMC free article] [PubMed] [Google Scholar]
  38. Waldo F. B. Is Henoch-Schönlein purpura the systemic form of IgA nephropathy? Am J Kidney Dis. 1988 Nov;12(5):373–377. doi: 10.1016/s0272-6386(88)80028-3. [DOI] [PubMed] [Google Scholar]
  39. Yamamoto K., Johnston R. B., Jr Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages. J Exp Med. 1984 Feb 1;159(2):405–416. doi: 10.1084/jem.159.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. van den Wall Bake A. W., Daha M. R., Haaijman J. J., Radl J., van der Ark A., van Es L. A. Elevated production of polymeric and monomeric IgA1 by the bone marrow in IgA nephropathy. Kidney Int. 1989 Jun;35(6):1400–1404. doi: 10.1038/ki.1989.139. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES