Slp is an Essential Component of an EDTA-resistant Activation Pathway of Mouse Complement

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Nov 15

PMID 1438267

Citations 9

Authors

C W van den Berg

P Demant

P C Aerts

H Van Dijk

Affiliations

Soon will be listed here.

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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References

Ferreira A, NUSSENZWEIG V, Gigli I . Structural and functional differences between the H-2 controlled Ss and Slp proteins. J Exp Med. 1978; 148(5):1186-97. PMC: 2185059. DOI: 10.1084/jem.148.5.1186. View

Atkinson J, McGinnis K, Shreffler D . Development and characterization of a hemolytic assay for mouse C4. J Immunol Methods. 1980; 33(4):351-68. DOI: 10.1016/0022-1759(80)90005-8. View

Hansen T, Shreffler D . Characterization of a constitutive variant of the murine serum protein allotype, Slp. J Immunol. 1976; 117(5 Pt 1):1507-13. View

van den Berg C, Aerts P, Van Dijk H . C1-inhibitor prevents PEG fractionation-induced, EDTA-resistant activation of mouse complement. Mol Immunol. 1992; 29(3):363-9. DOI: 10.1016/0161-5890(92)90023-q. View

Masaki T, Matsumoto M, Yasuda R, Levine R, 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; 147(3):927-32. View

van den Berg C, Aerts P, Van Dijk H . Functional assay of C5-activating and nonactivating cobra venom factor preparations in the mouse system. J Immunol Methods. 1990; 133(2):199-206. DOI: 10.1016/0022-1759(90)90360-8. View

DODDS A, Law S . The complement component C4 of mammals. Biochem J. 1990; 265(2):495-502. PMC: 1136911. DOI: 10.1042/bj2650495. View

Stief T, Aab A, HEIMBURGER N . Oxidative inactivation of purified human alpha-2-antiplasmin, antithrombin III, and C1-inhibitor. Thromb Res. 1988; 49(6):581-9. DOI: 10.1016/0049-3848(88)90255-1. View

Bruisten S, Skamene E, Demant P . Haplotype-specific interactions of non-H-2-linked genetic factors controlling the mouse C4 and Slp protein levels. Genetics. 1989; 121(4):795-801. PMC: 1203662. DOI: 10.1093/genetics/121.4.795. View

10.

Ogata R, Cooper N, Bradt B, Mathias P, Picchi M . 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; 86(14):5575-9. PMC: 297665. DOI: 10.1073/pnas.86.14.5575. View

11.

van den Berg C, Van Dijk H, Capel P . Rapid isolation and characterization of native mouse complement components C3 and C5. J Immunol Methods. 1989; 122(1):73-8. DOI: 10.1016/0022-1759(89)90336-0. View

12.

Bruisten S, 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. View

13.

PEMBERTON P, Harrison R, LACHMANN P, Carrell R . The structural basis for neutrophil inactivation of C1 inhibitor. Biochem J. 1989; 258(1):193-8. PMC: 1138340. DOI: 10.1042/bj2580193. View

14.

Shreffler D . Seventy-five years of immunology: the view from the MHC. J Immunol. 1988; 141(6):1791-8. View

15.

Van Dijk H, de Vos Burchart H, van Leeuwen M, Willers J . EDTA-resistant activation of the terminal route of mouse complement after partial precipitation of serum with polyethylene glycol. Immunol Lett. 1986; 12(5-6):281-8. DOI: 10.1016/0165-2478(86)90031-3. View

16.

Beekhuizen H, Van Dijk H, Willers J . Study on the pre-haemolytic complex formed upon polyethylene glycol-induced activation of mouse complement. Immunol Lett. 1986; 14(1):69-73. DOI: 10.1016/0165-2478(86)90023-4. View

17.

Nonaka M, Nakayama K, Yeul Y, 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; 136(8):2989-93. View

18.

Beukelman C, Aerts P, Van Dijk H, Willers J . A one-step isolation procedure for phospholipase A2-free cobra venom factor by fast protein liquid chromatography. J Immunol Methods. 1987; 97(1):119-22. DOI: 10.1016/0022-1759(87)90113-x. View

19.

Ogata R, Sepich D . Murine sex-limited protein: complete cDNA sequence and comparison with murine fourth complement component. J Immunol. 1985; 135(6):4239-44. View

20.

Danoff T, Goldman M, Goldman J . Murine sex-limited protein expression requires androgens and pituitary hormones. Immunogenetics. 1986; 23(1):7-10. DOI: 10.1007/BF00376515. View