Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1967 May 1;125(5):921–946. doi: 10.1084/jem.125.5.921

COMPLEMENT AS A MEDIATOR OF INFLAMMATION

II. BIOLOGICAL PROPERTIES OF ANAPHYLATOXIN PREPARED WITH PURIFIED COMPONENTS OF HUMAN COMPLEMENT

W Dias da Silva 1, Irwin H Lepow 1
PMCID: PMC2138204  PMID: 4960742

Abstract

Interaction in free solution of highly purified preparations of human C'1 esterase, C'4, C'2, and C'3, in the presence of Mg2+, resulted in rapid generation of an activity indistinguishable by biological criteria from anaphylatoxin. The formation of anaphylatoxin was associated with immunoelectrophoretic conversion of C'3 to anodically faster migrating proteins and was unaffected by the presence or absence of added C'5. The biological properties of human anaphylatoxin prepared in this manner include: contraction and desensitization of isolated guinea pig ileum, failure to contract isolated rat uterus, enhancement of vascular permeability in guinea pig skin, degranulation of mast cells in guinea pig mesentery preparations, and liberation of histamine from suspensions of rat peritoneal mast cells. The smooth muscle-contracting and permeability enhancing properties were fully blocked by an antihistaminic drug, triprolidine. No cross-desensitizing activity on guinea pig ileum was demonstrable between rat and human or guinea pig and human anaphylatoxins but a closer biological relationship between rat and guinea pig anaphylatoxins was observed. It is concluded that anaphylatoxin is a product of the complement system. Its possible relationship to apparently similar activities currently being obtained in other laboratories has been discussed.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

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

  1. Austen K. F., Becker E. L. Mechanisms of immunologic injury of rat peritoneal mast cells. II. Complement requirement and phosphonate ester inhibition of release of histamine by rabbit anti-rat gamma globulin. J Exp Med. 1966 Sep 1;124(3):397–416. doi: 10.1084/jem.124.3.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dias da Silva W., Lepow I. H. Anaphylatoxin formation by purified human C'1 esterase. J Immunol. 1965 Dec;95(6):1080–1089. [PubMed] [Google Scholar]
  3. FELDBERG W., TALESNIK J. Reduction of tissue histamine by compound 48/80. J Physiol. 1953 Jun 29;120(4):550–568. doi: 10.1113/jphysiol.1953.sp004917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. GREISMAN S. E. The role of anaphylatoxin during in vitro anaphylaxis. J Immunol. 1958 Sep;81(3):214–219. [PubMed] [Google Scholar]
  5. HAINES A. L., LEPOW I. H. STUDIES ON HUMAN C'1-ESTERASE. I. PURIFICATION AND ENZYMATIC PROPERTIES. J Immunol. 1964 Mar;92:456–467. [PubMed] [Google Scholar]
  6. HAINES A. L., LEPOW I. H. STUDIES ON HUMAN C'1-ESTERASE. II. FUNCTION OF PURIFIED C'1-ESTERASE IN THE HUMAN COMPLEMENT SYSTEM. J Immunol. 1964 Mar;92:468–478. [PubMed] [Google Scholar]
  7. KENT J. F., OTERO A. G., HARRIGAN R. E. Relative specificity of serologic tests for syphilis in Mycobacterium leprae infection. Am J Clin Pathol. 1957 May;27(5):539–545. doi: 10.1093/ajcp/27.5.539. [DOI] [PubMed] [Google Scholar]
  8. LEPOW I. H., LEON M. A. Interaction of a serum inhibitor of C'I-esterase with intermediate complexes of the immune haemolytic system. I. Specificity of inhibition of C'I activity associated with intermediate complexes. Immunology. 1962 Mar;5:222–234. [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. LEPOW I. H. Nonspecific factors in immunity and hypersensitivity. J Allergy. 1957 Jan;28(1):52–61. doi: 10.1016/0021-8707(57)90070-9. [DOI] [PubMed] [Google Scholar]
  11. LEPOW I. H., RATNOFF O. D., ROSEN F. S., PILLEMER L. Observations on a pro-esterase associated with partially purified first component of human complement (C'1). Proc Soc Exp Biol Med. 1956 May;92(1):32–37. doi: 10.3181/00379727-92-22376. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. MILES A. A., WILHELM D. L. Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. I. An activable permeability factor and its inhibitor in guinea-pig serum. Br J Exp Pathol. 1955 Feb;36(1):71–81. [PMC free article] [PubMed] [Google Scholar]
  14. MOTA I. The mechanism of action of anaphylatoxin. Its effect on guinea pig mast cells. Immunology. 1959 Oct;2:403–413. [PMC free article] [PubMed] [Google Scholar]
  15. MOTA I., da SILVA W. The anti-anaphylactic and histamine-releasing properties of the antihistamines. Their effect on the mast cells. Br J Pharmacol Chemother. 1960 Sep;15:396–404. doi: 10.1111/j.1476-5381.1960.tb01262.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MUELLER-EBERHARD H. J., BIRO C. E. ISOLATION AND DESCRIPTION OF THE FOURTH COMPONENT OF HUMAN COMPLEMENT. J Exp Med. 1963 Sep 1;118:447–466. doi: 10.1084/jem.118.3.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. MUELLER-EBERHARD H. J., LEPOW I. H. C'1 ESTERASE EFFECT ON ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF THE FOURTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 May 1;121:819–833. doi: 10.1084/jem.121.5.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MULLER-EBERHARD H. J. A new supporting medium for preparative electrophoresis. Scand J Clin Lab Invest. 1960;12:33–37. [PubMed] [Google Scholar]
  19. Muller-Eberhard H. J., Nilsson U. R., Dalmasso A. P., Polley M. J., Calcott M. A. A molecular concept of immune cytolysis. Arch Pathol. 1966 Sep;82(3):205–217. [PubMed] [Google Scholar]
  20. NAFF G. B., PENSKY J., LEPOW I. H. THE MACROMOLECULAR NATURE OF THE FIRST COMPONENT OF HUMAN COMPLEMENT. J Exp Med. 1964 Apr 1;119:593–613. doi: 10.1084/jem.119.4.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. NILSSON U. R., MUELLER-EBERHARD H. J. ISOLATION OF BETA IF-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 Aug 1;122:277–298. doi: 10.1084/jem.122.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. OSLER A. G., RANDALL H. G., HILL B. M., OVARY Z. Studies on the mechanism of hypersensitivity phenomena. III. The participation of complement in the formation of anaphylatoxin. J Exp Med. 1959 Aug 1;110(2):311–339. doi: 10.1084/jem.110.2.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. RATNOFF O. D., LEPOW I. H. COMPLEMENT AS A MEDIATOR OF INFLAMMATION. ENHANCEMENT OF VASCULAR PERMEABILITY BY PURIFIED HUMAN C'1 ESTERASE. J Exp Med. 1963 Nov 1;118:681–698. doi: 10.1084/jem.118.5.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. SMINK R. D., Jr, ABERNETHY R. W., RATNOFF O. D., LEPOW I. H. ENHANCEMENT OF VASCULAR PERMEABILITY BY MIXTURES OF C'1 ESTERASE AND NORMAL SERUM. Proc Soc Exp Biol Med. 1964 Jun;116:280–283. doi: 10.3181/00379727-116-29226. [DOI] [PubMed] [Google Scholar]
  25. UNGAR G. Biochemical mechanism of the allergic reaction. Int Arch Allergy Appl Immunol. 1953;4(4):258–281. doi: 10.1159/000228030. [DOI] [PubMed] [Google Scholar]
  26. Vogt W., Schmidt G. Abtrennung des anaphylatoxinbildenden Prinzips aus Cobragift von anderen Giftkomponenten. Experientia. 1964 Apr 15;20(4):207–208. doi: 10.1007/BF02135403. [DOI] [PubMed] [Google Scholar]
  27. YACHNIN S. THE HEMOLYSIS OF RED CELLS FROM PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA BY PARTIALLY PURIFIED SUB-COMPONENTS OF THE THIRD COMPLEMENT COMPONENT. J Clin Invest. 1965 Sep;44:1534–1546. doi: 10.1172/JCI105260. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES