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. 1985 Apr;54(4):801–810.

In vivo degradation of rat C1q induced by intravenous injection of soluble IgG aggregates.

R Veerhuis, L A van Es, M R Daha
PMCID: PMC1453567  PMID: 3872261

Abstract

Immune complexes are able to bind and activate the first component of complement, C1. Upon activation of C1, C1r and C1s are rapidly inactivated by C1-In which also forms a complex with these two subcomponents, resulting in their release from C1-immune aggregate complexes. The fate of C1q after the binding C1 to immune complexes in vivo is not clear and, therefore the clearance of radiolabelled rat C1q was investigated in normal rats and in rats receiving soluble aggregated human IgG. 125I-labelled rat C1q was cleared with a half-life (T 1/2) of 12.4 hr in normal rats. Injection of AIgG into rats that had previously received 125I-C1q accelerated the clearance of 125I-C1q, resulting, finally, in a T 1/2 of 53 min. The levels of circulating endogenous C1q were also followed using haemolytic titrations and immunochemical measurements. Directly after injection of AIgG into rats, there was a rapid decrease in C1q haemolytic activity to less than 25% of the initial value after 10 min. The rate of disappearance of C1q antigen, was, however, much slower, the lowest concentration being 30% at 2 hr. C1q haemolytic activity and the C1q antigen level returned to virtually normal values after 24 hr. Plasma samples were taken at different time intervals after the injection of AIgG and subjected to gel filtration on Sephacryl S-400 columns. It was found that, in the 10 min samples, C1q antigen and C1q haemolytic activity, each with an estimated molecular weight (MW) of 400,000, were detected together. In addition, there was C1q antigen with a MW of less than 69,000 without C1q haemolytic activity. SDS-PAGE analysis of the various serum samples indicated that the low MW C1q antigen had an apparent MW of 25,000. Measurement of uptake of 125I-C1q in various organs indicated that the main site of clearance of 125I-C1q is the liver.

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Selected References

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  1. Avrameas S., Ternynck T. Peroxidase labelled antibody and Fab conjugates with enhanced intracellular penetration. Immunochemistry. 1971 Dec;8(12):1175–1179. doi: 10.1016/0019-2791(71)90395-8. [DOI] [PubMed] [Google Scholar]
  2. Cochrane C. G., Koffler D. Immune complex disease in experimental animals and man. Adv Immunol. 1973;16(0):185–264. doi: 10.1016/s0065-2776(08)60298-9. [DOI] [PubMed] [Google Scholar]
  3. Doekes G., Vanes L. A., Daha M. R. Influence of aggregate size on the binding and activation of the first component of human complement by soluble IgG aggregates. Immunology. 1982 Apr;45(4):705–713. [PMC free article] [PubMed] [Google Scholar]
  4. Doekes G., van Es L. A., Daha M. R. Activation of C1 by soluble IgG aggregates as detected by a novel one-step hemolytic assay that specifically measures the proenzyme form of C1s. J Immunol. 1983 Oct;131(4):1924–1929. [PubMed] [Google Scholar]
  5. 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]
  6. Hack C. E., Hannema A. J., Eerenberg-Belmer A. J., Out T. A., Aalberse R. C. A C1-inhibitor-complex assay (INCA): a method to detect C1 activation in vitro and in vivo. J Immunol. 1981 Oct;127(4):1450–1453. [PubMed] [Google Scholar]
  7. Hannema A. J., Kluin-Nelemans J. C., Hack C. E., Eerenberg-Belmer A. J., Mallée C., van Helden H. P. SLE like syndrome and functional deficiency of C1q in members of a large family. Clin Exp Immunol. 1984 Jan;55(1):106–114. [PMC free article] [PubMed] [Google Scholar]
  8. Kauffmann R. H., Van Es L. A., Daha M. R. Aggregated human immunoglobulin G stabilized by albumin: a standard for immune complex detection. J Immunol Methods. 1979;31(1-2):11–22. doi: 10.1016/0022-1759(79)90281-3. [DOI] [PubMed] [Google Scholar]
  9. Kilchherr E., Fuchs H., Tschopp J., Engel J. Dissociation of C1 and concentration dependence of its activation kinetics. Mol Immunol. 1982 May;19(5):683–691. doi: 10.1016/0161-5890(82)90370-4. [DOI] [PubMed] [Google Scholar]
  10. Kohler P. F., Müller-Eberhard H. J. Metabolism of human C1q. Studies in hypogammaglobulinemia, myeloma, and systemic lupus erythematosus. J Clin Invest. 1972 Apr;51(4):868–875. doi: 10.1172/JCI106881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kolb W. P., Kolb L. M., Podack E. R. C1q: isolation from human serum in high yield by affinity chromatography and development of a highly sensitive hemolytic assay. J Immunol. 1979 May;122(5):2103–2111. [PubMed] [Google Scholar]
  12. LEPOW I. H., NAFF G. B., TODD E. W., PENSKY J., HINZ C. F. Chromatographic resolution of the first component of human complement into three activities. J Exp Med. 1963 Jun 1;117:983–1008. doi: 10.1084/jem.117.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Laurell A. B., Johnson U., Mårtensson U., Sjöholm A. G. Formation of complexes composed of C1r, C1s, and C1 inactivator in human serum on activation of C1. Acta Pathol Microbiol Scand C. 1978 Dec;86C(6):299–306. doi: 10.1111/j.1699-0463.1978.tb02594.x. [DOI] [PubMed] [Google Scholar]
  15. Lin T. Y., Fletcher D. S. Activation of a complex of C1r and C1s subcomponents of human complement C1 by the third subcomponent C1q. J Biol Chem. 1980 Aug 25;255(16):7756–7762. [PubMed] [Google Scholar]
  16. MULLER-EBERHARD H. J., KUNKEL H. G. Isolation of a thermolabile serum protein which precipitates gamma-globulin aggregates and participates in immune hemolysis. Proc Soc Exp Biol Med. 1961 Feb;106:291–295. doi: 10.3181/00379727-106-26313. [DOI] [PubMed] [Google Scholar]
  17. Müller W., Hanauske-Abel H., Loos M. Biosynthesis of the first component of complement by human and guinea pig peritoneal macrophages: evidence for an independent production of the C1 subunits. J Immunol. 1978 Oct;121(4):1578–1584. [PubMed] [Google Scholar]
  18. Porter R. R., Reid K. B. The biochemistry of complement. Nature. 1978 Oct 26;275(5682):699–704. doi: 10.1038/275699a0. [DOI] [PubMed] [Google Scholar]
  19. Reid K. B., Thompson R. A. Characterization of a non-functional form of C1q found in patients with a genetically linked deficiency of C1q activity. Mol Immunol. 1983 Oct;20(10):1117–1125. doi: 10.1016/0161-5890(83)90121-9. [DOI] [PubMed] [Google Scholar]
  20. Sim R. B., Arlaud G. J., Colomb M. G. C1 inhibitor-dependent dissociation of human complement component C1 bound to immune complexes. Biochem J. 1979 Jun 1;179(3):449–457. doi: 10.1042/bj1790449a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tenner A. J., Cooper N. R. Analysis of receptor-mediated C1q binding to human peripheral blood mononuclear cells. J Immunol. 1980 Oct;125(4):1658–1664. [PubMed] [Google Scholar]
  22. Tenner A. J., Lesavre P. H., Cooper N. R. Purification and radiolabeling of human C1q. J Immunol. 1981 Aug;127(2):648–653. [PubMed] [Google Scholar]
  23. Thorell J. I., Larsson I. Lactoperoxidase coupled to polyacrylamide for radio-iodination of proteins to high specific activity. Immunochemistry. 1974 Apr;11(4):203–206. doi: 10.1016/0019-2791(74)90329-2. [DOI] [PubMed] [Google Scholar]
  24. Valet G., Cooper N. R. Isolation and characterization of the proenzyme form of the C1r subunit of the first complement component. J Immunol. 1974 May;112(5):1667–1673. [PubMed] [Google Scholar]
  25. Ziccardi R. J., Cooper N. R. Active disassembly of the first complement component, C-1, by C-1 inactivator. J Immunol. 1979 Aug;123(2):788–792. [PubMed] [Google Scholar]
  26. Ziccardi R. J., Cooper N. R. Physicochemical and functional characterization of the C1r subunit of the first complement component. J Immunol. 1976 Feb;116(2):496–503. [PubMed] [Google Scholar]

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