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. 1979 Oct;76(10):5299–5302. doi: 10.1073/pnas.76.10.5299

C4a: the third anaphylatoxin of the human complement system.

J P Gorski, T E Hugli, H J Müller-Eberhard
PMCID: PMC413129  PMID: 291947

Abstract

The activation peptide C4a was isolated from C1s-cleaved C4, the fourth component of complement. The peptide appeared to be homogeneous by electrophoresis on cellulose acetate and by polyacrylamide gel electrophoresis. C4a has a molecular weight of 8650 and an electrophoretic mobility at pH 8.6 of +2.1 x 10(-5) cm2V-1 sec-1. Carboxypeptidase B released approximately 1 mol of arginine per mol of C4a. The partial COOH-terminal sequence was determined to be Leu-Gln-Arg-COOH. The isolated C4a was spasmogenic for guinea pig ileum at a concentration of 1 microM and it desensitized the muscle (i.e., produced tachyphylaxis) with respect to human C3a anaphylatoxin (at 0.33 microM) but not with respect to human C5a anaphylatoxin. Increased vascular permeability was observed in human skin after intradermal injection of 1 nmol of C4a, as evidenced by immediate erythema and edema formation. The spasmogenic, tachyphylactic, and vascular activities of C4a were abrogated by removal of the COOH-terminal arginine, a property that is characteristic also of the C3a and C5a anaphylatoxins. Contamination of C4a with either C3a or C5a has been ruled out by using radioimmunoassays for these peptides. Although C4a is considerably less active than are C3a and C5a, the present observations suggest that C4a constitutes a heretofore unrecognized anaphylatoxin that is related biologically and chemically to the activation peptides of C3 and C5.

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Selected References

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

  1. Bolotin C., Morris S., Tack B., Prahl J. Purification and structural analysis of the fourth component of human complement. Biochemistry. 1977 May 3;16(9):2008–2015. doi: 10.1021/bi00628a039. [DOI] [PubMed] [Google Scholar]
  2. Chenoweth D. E., Rowe J. G., Hugli T. E. A modified method for chemotaxis under agarose. J Immunol Methods. 1979;25(4):337–353. doi: 10.1016/0022-1759(79)90026-7. [DOI] [PubMed] [Google Scholar]
  3. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fernandez H. N., Henson P. M., Otani A., Hugli T. E. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed] [Google Scholar]
  5. Fernandez H. N., Hugli T. E. Partial characterization of human C5a anaphylatoxin. I. Chemical description of the carbohydrate and polypeptide prtions of human C5a. J Immunol. 1976 Nov;117(5 Pt 1):1688–1694. [PubMed] [Google Scholar]
  6. Fernandez H. N., Hugli T. E. Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. J Biol Chem. 1978 Oct 10;253(19):6955–6964. [PubMed] [Google Scholar]
  7. Fernandez H. N., Huglij T. E. Chemical evidence for common genetic ancestry of complement components C3 and C5. J Biol Chem. 1977 Mar 10;252(5):1826–1828. [PubMed] [Google Scholar]
  8. Hugli T. E., Erickson B. W. Synthetic peptides with the biological activities and specificity of human C3a anaphylatoxin. Proc Natl Acad Sci U S A. 1977 May;74(5):1826–1830. doi: 10.1073/pnas.74.5.1826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hugli T. E., Morgan W. T., Müller-Eberhard H. J. Circular dichroism of C3a anaphylatoxin. Effects of pH, heat, guanidinium chloride, and mercaptoethanol on conformation and function. J Biol Chem. 1975 Feb 25;250(4):1479–1483. [PubMed] [Google Scholar]
  10. Hugli T. E., Vallota E. H., Müller-Eberhard H. J. Purification and partial characterization of human and porcine C3a anaphylatoxin. J Biol Chem. 1975 Feb 25;250(4):1472–1478. [PubMed] [Google Scholar]
  11. Johnson A. R., Hugli T. E., Müller-Eberhard H. J. Release of histamine from rat mast cells by the complement peptides C3a and C5a. Immunology. 1975 Jun;28(6):1067–1080. [PMC free article] [PubMed] [Google Scholar]
  12. Morgan W. T., Vallota E. H., Müller-Eberhard H. J. Circular dichroism of C5a anaphylatoxin of porcine complement. Biochem Biophys Res Commun. 1974 Apr 8;57(3):572–577. doi: 10.1016/0006-291x(74)90584-1. [DOI] [PubMed] [Google Scholar]
  13. Snyderman R., Shin H. S., Hausman M. H. A chemotactic factor for mononuclear leukocytes. Proc Soc Exp Biol Med. 1971 Nov;138(2):387–390. doi: 10.3181/00379727-138-35903. [DOI] [PubMed] [Google Scholar]
  14. Valet G., Cooper N. R. Isolation and characterization of the proenzyme form of the C1s subunit of the first complement component. J Immunol. 1974 Jan;112(1):339–350. [PubMed] [Google Scholar]
  15. Wuepper K. D., Bokisch V. A., Müller-Eberhard H. J., Stoughton R. B. Cutaneous responses to human C 3 anaphylatoxin in man. Clin Exp Immunol. 1972 May;11(1):13–20. [PMC free article] [PubMed] [Google Scholar]

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