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. 1979 Apr 1;149(4):870–882. doi: 10.1084/jem.149.4.870

Bactericidal activity of the alternative complement pathway generated from 11 isolated plasma proteins

PMCID: PMC2184846  PMID: 372483

Abstract

Exposure of E. coli K12 W1485 to the cytolytic alternative pathway assembled from the 11 isolated pathway proteins resulted in killing of the bacteria, as evidenced by loss of viability. Lysis of the bacteria required introduction of lysozyme into the reaction mixture. The time- course and dose dependency of bacteriolysis in the isolated system were identical to those in C4-depleted serum. The bacteriolytic activity of the pathway was highly dependent on the concentration of the pathway proteins and became insignificant at 1:16 physiological concentration. Electron microscopic visualization of killed and of lysed bacteria revealed numerous complement membrane lesions and partial disintegration of the outer phospholipid membrane. Scanning electron microscopy showed that killed bacteria were enlarged, partially collapsed and exhibited irregular surface protrusions. Lysed bacteria were fragmented and appeared polymorphic. This study demonstrates that the alternative pathway, in absence of immunoglobulins, has the potential or eradicating gram-negative bacteria.

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Selected References

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

  1. David G. S., Reisfeld R. A. Protein iodination with solid state lactoperoxidase. Biochemistry. 1974 Feb 26;13(5):1014–1021. doi: 10.1021/bi00702a028. [DOI] [PubMed] [Google Scholar]
  2. Götze O., Medicus R. G., Müller-Eberhard H. J. Alternative pathway of complement: nonenzymatic, reversible transition of precursor to active properdin. J Immunol. 1977 Feb;118(2):525–532. [PubMed] [Google Scholar]
  3. 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]
  4. Hadding U., Müller-Eberhard H. J. The ninth component of human complement: isolation, description and mode of action. Immunology. 1969 Jun;16(6):719–735. [PMC free article] [PubMed] [Google Scholar]
  5. Inoue K., Takamizawa A., Yano K., Amano T. Chemical studies on damages of Escherichia coli by the immune bactericidal reaction. I. Release and degradation of phospholipids from damaged bacteria. Biken J. 1974 Dec;17(4):127–134. [PubMed] [Google Scholar]
  6. Klob W. P., Müller-Eberhard H. J. The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). J Exp Med. 1976 May 1;143(5):1131–1139. doi: 10.1084/jem.143.5.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. LEON M. A. Quantitative studies on the properdin-complement system. J Exp Med. 1956 Mar 1;103(3):285–293. doi: 10.1084/jem.103.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. MICHAEL J. G., WHITBY J. L., LANDY M. Studies on natural antibodies to gram-negative bacteria. J Exp Med. 1962 Jan 1;115:131–146. doi: 10.1084/jem.115.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. OSAWA E., MUSCHEL L. H. The bactericidal action of normal serum and the properdin system. J Immunol. 1960 Feb;84:203–212. [PubMed] [Google Scholar]
  10. PILLEMER L., BLUM L., LEPOW I. H., ROSS O. A., TODD E. W., WARDLAW A. C. The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science. 1954 Aug 20;120(3112):279–285. doi: 10.1126/science.120.3112.279. [DOI] [PubMed] [Google Scholar]
  11. Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution. J Exp Med. 1977 Jul 1;146(1):257–270. doi: 10.1084/jem.146.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Podack E. R., Kolb W. P., Müller-Eberhard H. J. Purification of the sixth and seventh component of human complement without loss of hemolytic activity. J Immunol. 1976 Feb;116(2):263–269. [PubMed] [Google Scholar]
  13. Reed W. P., Albright E. L. Serum factors responsible for killing of Shigella. Immunology. 1974 Jan;26(1):205–215. [PMC free article] [PubMed] [Google Scholar]
  14. Root R. K., Ellman L., Frank M. M. Bactericidal and opsonic properties of C4-deficient guinea pig serum. J Immunol. 1972 Sep;109(3):477–486. [PubMed] [Google Scholar]
  15. Rowley D. Sensitivity of rough gram-negative bacteria to the bactericidal action of serum. J Bacteriol. 1968 May;95(5):1647–1650. doi: 10.1128/jb.95.5.1647-1650.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. STERZL J., KOSTKA J., LANC A. Development of bactericidal properties against gram-negative organisms in the serum of young animals. Folia Microbiol (Praha) 1962 May;7:162–174. doi: 10.1007/BF02928237. [DOI] [PubMed] [Google Scholar]
  17. Sandberg A. L., Osler A. G. Dual pathways of complement interaction with guinea pig immunoglobulins. J Immunol. 1971 Nov;107(5):1268–1273. [PubMed] [Google Scholar]
  18. Schreiber R. D., Götze O., Müller-Eberhard H. J. Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function. J Exp Med. 1976 Oct 1;144(4):1062–1075. doi: 10.1084/jem.144.4.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schreiber R. D., Müller-Eberhard H. J. Assembly of the cytolytic alternative pathway of complement from 11 isolated plasma proteins. J Exp Med. 1978 Dec 1;148(6):1722–1727. doi: 10.1084/jem.148.6.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schreiber R. D., Pangburn M. K., Lesavre P. H., Müller-Eberhard H. J. Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3948–3952. doi: 10.1073/pnas.75.8.3948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Skarnes R. C. Humoral bactericidal systems: nonspecific and specific mechanisms. Infect Immun. 1978 Feb;19(2):515–522. doi: 10.1128/iai.19.2.515-522.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Spitznagel J. K. Normal serum cytotoxicity for P32-labeled smooth Enterobacteriaceae. 3. Isolation of a gammag normal antibody and characterization of other serum factors causing P32 loss. J Bacteriol. 1966 Jan;91(1):401–408. doi: 10.1128/jb.91.1.401-408.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tack B. D., Prahl J. W. Third component of human complement: purification from plasma and physicochemical characterization. Biochemistry. 1976 Oct 5;15(20):4513–4521. doi: 10.1021/bi00665a028. [DOI] [PubMed] [Google Scholar]
  24. Tseng B. Y., Marvin D. A. Filamentous bacterial viruses. V. Asymmetric replication of fd duplex deoxyribonucleic acid. J Virol. 1972 Sep;10(3):371–383. doi: 10.1128/jvi.10.3.371-383.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. WARDLAW A. C., PILLEMER L. The properdin system and immunity. V. The bactericidal activity of the properdin system. J Exp Med. 1956 May 1;103(5):553–575. doi: 10.1084/jem.103.5.553. [DOI] [PMC free article] [PubMed] [Google Scholar]

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