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. 1992 Nov 15;89(22):10711–10715. doi: 10.1073/pnas.89.22.10711

Slp is an essential component of an EDTA-resistant activation pathway of mouse complement.

C W van den Berg 1, P Démant 1, P C Aerts 1, H Van Dijk 1
PMCID: PMC50411  PMID: 1438267

Abstract

Slp (sex-limited protein) is a mouse serum protein encoded by a major histocompatibility complex class III gene. It is considered to be a product of a duplicated complement component C4 gene, but without functional activity. Originally it has been found expressed only in adult males with the S region of the H-2d or H-2s haplotype. In this report we present evidence that Slp is involved in a form of mouse complement activation that occurs after fractionation of serum by polyethylene glycol precipitation. This activation pathway is EDTA-resistant (i.e., independent of classical and alternative pathway activation), is regulated by C1 inhibitor, and leads to the generation of hemolytically active membrane attack complexes. A positive correlation between this EDTA-resistant mouse complement activity and reported Slp levels was found. Direct evidence for a functional role of Slp came from substitution experiments in which purified Slp induced hemolytic activity in polyethylene glycol-fractionated, Slp-deficient mouse serum. Selective depletion of other complement components suggested a role for C1s-, C2, and C5, but not C3, in the Slp-dependent complement activation. A model for this type of mouse complement activation is presented.

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Selected References

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

  1. Atkinson J. P., Karp D. R., Seeskin E. P., Killion C. C., Rosa P. A., Newell S. L., Shreffler D. C. H-2 S region determined polymorphic variants of the C4, Slp, C2, and B complement proteins: a compilation. Immunogenetics. 1982;16(6):617–623. doi: 10.1007/BF00372032. [DOI] [PubMed] [Google Scholar]
  2. Atkinson J. P., McGinnis K., Shreffler D. Development and characterization of a hemolytic assay for mouse C4. J Immunol Methods. 1980;33(4):351–368. doi: 10.1016/0022-1759(80)90005-8. [DOI] [PubMed] [Google Scholar]
  3. Beekhuizen H., van Dijk H., Willers J. M. Study on the pre-haemolytic complex formed upon polyethylene glycol-induced activation of mouse complement. Immunol Lett. 1986 Nov 17;14(1):69–73. doi: 10.1016/0165-2478(86)90023-4. [DOI] [PubMed] [Google Scholar]
  4. Beukelman C. J., Aerts P. C., Van Dijk H., Willers J. M. A one-step isolation procedure for phospholipase A2-free cobra venom factor by fast protein liquid chromatography. J Immunol Methods. 1987 Feb 26;97(1):119–122. doi: 10.1016/0022-1759(87)90113-x. [DOI] [PubMed] [Google Scholar]
  5. Bruisten S. M., Demant P. Regulation of expression of mouse C4 and Slp genes by non-H-2-linked genes. Immunogenetics. 1989;29(1):6–13. doi: 10.1007/BF02341607. [DOI] [PubMed] [Google Scholar]
  6. Bruisten S. M., Skamene E., Demant P. Haplotype-specific interactions of non-H-2-linked genetic factors controlling the mouse C4 and Slp protein levels. Genetics. 1989 Apr;121(4):795–801. doi: 10.1093/genetics/121.4.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Danoff T. M., Goldman M. B., Goldman J. N. Murine sex-limited protein expression requires androgens and pituitary hormones. Immunogenetics. 1986;23(1):7–10. doi: 10.1007/BF00376515. [DOI] [PubMed] [Google Scholar]
  8. Dodds A. W., Law S. K. The complement component C4 of mammals. Biochem J. 1990 Jan 15;265(2):495–502. doi: 10.1042/bj2650495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ferreira A., Nussenzweig V., Gigli I. Structural and functional differences between the H-2 controlled Ss and Slp proteins. J Exp Med. 1978 Nov 1;148(5):1186–1197. doi: 10.1084/jem.148.5.1186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  11. Hansen T. H., Shreffler D. C. Characterization of a constitutive variant of the murine serum protein allotype, Slp. J Immunol. 1976 Nov;117(5 Pt 1):1507–1513. [PubMed] [Google Scholar]
  12. Jessen T. E., Barkholt V., Welinder K. G. A simple alternative pathway for hemolytic assay of human complement component C3 using methylamine-treated plasma. J Immunol Methods. 1983 May 27;60(1-2):89–100. doi: 10.1016/0022-1759(83)90338-1. [DOI] [PubMed] [Google Scholar]
  13. Kitamura H., Tsuboi M., Nagaki K. C56 formation in the reaction mixture of isolated complement components through the classical complement pathway. Int Arch Allergy Appl Immunol. 1985;78(1):101–107. doi: 10.1159/000233870. [DOI] [PubMed] [Google Scholar]
  14. Klerx J. P., Beukelman C. J., Van Dijk H., Willers J. M. Microassay for colorimetric estimation of complement activity in guinea pig, human and mouse serum. J Immunol Methods. 1983 Oct 14;63(2):215–220. doi: 10.1016/0022-1759(83)90425-8. [DOI] [PubMed] [Google Scholar]
  15. Law S. K., Dodds A. W., Porter R. R. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J. 1984 Aug;3(8):1819–1823. doi: 10.1002/j.1460-2075.1984.tb02052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Masaki T., Matsumoto M., Yasuda R., Levine R. P., Kitamura H., Seya T. A covalent dimer of complement C4b serves as a subunit of a novel C5 convertase that involves no C3 derivatives. J Immunol. 1991 Aug 1;147(3):927–932. [PubMed] [Google Scholar]
  17. Neoh S. H., Gordon T. P., Roberts-Thomson P. J. A simple one-step procedure for preparation of C1-deficient human serum. J Immunol Methods. 1984 Apr 27;69(2):277–280. doi: 10.1016/0022-1759(84)90325-9. [DOI] [PubMed] [Google Scholar]
  18. Nonaka M., Nakayama K., Yeul Y. D., Takahashi M. Complete nucleotide and derived amino acid sequences of sex-limited protein (Slp), nonfunctional isotype of the fourth component of mouse complement (C4). J Immunol. 1986 Apr 15;136(8):2989–2993. [PubMed] [Google Scholar]
  19. Ogata R. T., Cooper N. R., Bradt B. M., Mathias P., Picchi M. A. Murine complement component C4 and sex-limited protein: identification of amino acid residues essential for C4 function. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5575–5579. doi: 10.1073/pnas.86.14.5575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ogata R. T., Sepich D. S. Murine sex-limited protein: complete cDNA sequence and comparison with murine fourth complement component. J Immunol. 1985 Dec;135(6):4239–4244. [PubMed] [Google Scholar]
  21. Passmore H. C., Shreffler D. C. A sex-limited serum protein variant in the mouse: hormonal control of phenotypic expression. Biochem Genet. 1971 Apr;5(2):201–209. doi: 10.1007/BF00485645. [DOI] [PubMed] [Google Scholar]
  22. Pemberton P. A., Harrison R. A., Lachmann P. J., Carrell R. W. The structural basis for neutrophil inactivation of C1 inhibitor. Biochem J. 1989 Feb 15;258(1):193–198. doi: 10.1042/bj2580193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shreffler D. C. Seventy-five years of immunology: the view from the MHC. J Immunol. 1988 Sep 15;141(6):1791–1798. [PubMed] [Google Scholar]
  24. Shreffler D. C. The S region of the mouse major histocompatibility complex (H-2): genetic variation and functional role in complement system. Transplant Rev. 1976;32:140–167. doi: 10.1111/j.1600-065x.1976.tb00232.x. [DOI] [PubMed] [Google Scholar]
  25. Stief T. W., Aab A., Heimburger N. Oxidative inactivation of purified human alpha-2-antiplasmin, antithrombin III, and C1-inhibitor. Thromb Res. 1988 Mar 15;49(6):581–589. doi: 10.1016/0049-3848(88)90255-1. [DOI] [PubMed] [Google Scholar]
  26. Van den Berg C. W., Aerts P. C., Van Dijk H. Functional assay of C5-activating and nonactivating cobra venom factor preparations in the mouse system. J Immunol Methods. 1990 Oct 19;133(2):199–206. doi: 10.1016/0022-1759(90)90360-8. [DOI] [PubMed] [Google Scholar]
  27. Van den Berg C. W., Van Dijk H., Capel P. J. Rapid isolation and characterization of native mouse complement components C3 and C5. J Immunol Methods. 1989 Aug 15;122(1):73–78. doi: 10.1016/0022-1759(89)90336-0. [DOI] [PubMed] [Google Scholar]
  28. van Dijk H., de Vos Burchart H., van Leeuwen M., Willers J. M. EDTA-resistant activation of the terminal route of mouse complement after partial precipitation of serum with polyethylene glycol. Immunol Lett. 1986 Jun;12(5-6):281–288. doi: 10.1016/0165-2478(86)90031-3. [DOI] [PubMed] [Google Scholar]
  29. van den Berg C. W., Aerts P. C., van Dijk H. C1-inhibitor prevents PEG fractionation-induced, EDTA-resistant activation of mouse complement. Mol Immunol. 1992 Mar;29(3):363–369. doi: 10.1016/0161-5890(92)90023-q. [DOI] [PubMed] [Google Scholar]

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