Skip to main content
NCBI home page
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1986 Jan;23(1):56–61. doi: 10.1128/jcm.23.1.56-61.1986

Relationships between alternative complement pathway activation, C-reactive protein, and pneumococcal infection.

R A Rabinovitch, S M Koethe, J H Kalbfleisch, L C Preheim, M W Rytel
PMCID: PMC268572  PMID: 3700607

Abstract

In the absence of specific antibody, opsonization of Streptococcus pneumoniae may be mediated by the alternative complement pathway (AP) or by C-reactive protein (CRP) via C1 binding. To determine the role of these mechanisms in pneumococcal (PNC) disease, we studied 19 patients with differing severities of PNC infection. C4 and CRP levels and zymosan-induced consumption of 50% hemolytic complement (CH50) were measured in specimens obtained acutely and then weekly. In patients with complicated illness, the modified mean CH50 in acute sera was 178 +/- 57 U/ml, significantly lower than the mean CH50 of 331 +/- 80 U/ml in patients with uncomplicated illness (P less than 0.05). The values of the two groups on a given day approximated each other on days 7, 14, and 23. Consumption of complement by zymosan was also lower in acute sera of patients with complicated illness, with a mean value of 19 +/- 18 U/ml compared with 58 +/- 30 U/ml in those with uncomplicated illness (P less than 0.05). This difference was also seen on day 7 (P less than 0.05). Disease involving lower-numbered PNC serotypes (less than 10) correlated with reduced availability of AP factors in acute sera, independent of illness severity. Mean CRP levels were inversely related to zymosan-induced complement activation in patients with complicated illness. These data suggest that in vivo depletion of AP factors is significantly greater in patients with complicated illness and is associated with high CRP levels. CRP may enhance AP activation via C3 convertase generation and function with it as a preantibody host defense mechanism.

Full text

PDF
56

Selected References

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

  1. AUSTRIAN R., GOLD J. PNEUMOCOCCAL BACTEREMIA WITH ESPECIAL REFERENCE TO BACTEREMIC PNEUMOCOCCAL PNEUMONIA. Ann Intern Med. 1964 May;60:759–776. doi: 10.7326/0003-4819-60-5-759. [DOI] [PubMed] [Google Scholar]
  2. Bakker-Woudenberg I. A., de Jong-Hoenderop J. Y., Michel M. F. Efficacy of antimicrobial therapy in experimental rat pneumonia: effects of impaired phagocytosis. Infect Immun. 1979 Jul;25(1):366–375. doi: 10.1128/iai.25.1.366-375.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Claus D. R., Siegel J., Petras K., Osmand A. P., Gewurz H. Interactions of C-reactive protein with the first component of human complement. J Immunol. 1977 Jul;119(1):187–192. [PubMed] [Google Scholar]
  4. Coonrod J. D., Leach R. P. Antigenemia in fulminant pneumococcemia. Ann Intern Med. 1976 May;84(5):561–563. doi: 10.7326/0003-4819-84-5-561. [DOI] [PubMed] [Google Scholar]
  5. Coonrod J. D., Rylko-Bauer B. Complement levels in pneumococcal pneumonia. Infect Immun. 1977 Oct;18(1):14–22. doi: 10.1128/iai.18.1.14-22.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fine D. P., Marney S. R., Jr, Colley D. G., Sergent J. S., Des Prez R. M. C3 shunt activation in human serum chelated with EGTA. J Immunol. 1972 Oct;109(4):807–809. [PubMed] [Google Scholar]
  7. Fine D. P. Pneumococcal type-associated variability in alternate complement pathway activation. Infect Immun. 1975 Oct;12(4):772–778. doi: 10.1128/iai.12.4.772-778.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Giebink G. S., Verhoef J., Peterson P. K., Quie P. G. Opsonic requirements for phagocytosis of Streptococcus pneumoniae types VI, XVIII, XXIII, and XXV. Infect Immun. 1977 Nov;18(2):291–297. doi: 10.1128/iai.18.2.291-297.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gross G. N., Rehm S. R., Pierce A. K. The effect of complement depletion on lung clearance of bacteria. J Clin Invest. 1978 Aug;62(2):373–378. doi: 10.1172/JCI109138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Henson P. M., McCarthy K., Larsen G. L., Webster R. O., Giclas P. C., Dreisin R. B., King T. E., Shaw J. O. Complement fragments, alveolar macrophages, and alveolitis. Am J Pathol. 1979 Oct;97(1):93–110. [PMC free article] [PubMed] [Google Scholar]
  11. Hummell D. S., Berninger R. W., Tomasz A., Winkelstein J. A. The fixation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway. J Immunol. 1981 Oct;127(4):1287–1289. [PubMed] [Google Scholar]
  12. Johnston R. B., Jr The host response to invasion by Streptococcus pneumoniae: protection and the pathogenesis to tissue damage. Rev Infect Dis. 1981 Mar-Apr;3(2):282–288. doi: 10.1093/clinids/3.2.282. [DOI] [PubMed] [Google Scholar]
  13. Kaplan M. H., Volanakis J. E. Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol. 1974 Jun;112(6):2135–2147. [PubMed] [Google Scholar]
  14. Kenny G. E., Wentworth B. B., Beasley R. P., Foy H. M. Correlation of circulating capsular polysaccharide with bacteremia in pneumococcal pneumonia. Infect Immun. 1972 Oct;6(4):431–437. doi: 10.1128/iai.6.4.431-437.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mold C., Gewurz H. Inhibitory effect of C-reactive protein on alternative C pathway activation by liposomes and Streptococcus pneumoniae. J Immunol. 1981 Nov;127(5):2089–2092. [PubMed] [Google Scholar]
  16. Mufson M. A., Kruss D. M., Wasil R. E., Metzger W. I. Capsular types and outcome of bacteremic pneumococcal disease in the antibiotic era. Arch Intern Med. 1974 Sep;134(3):505–510. [PubMed] [Google Scholar]
  17. Polhill R. B., Jr, Newman S. L., Pruitt K. M., Johnston R. B., Jr Kinetic assessment of alternative complement pathway activity in a hemolytic system. II. Influence of antibody on alternative pathway activation. J Immunol. 1978 Jul;121(1):371–376. [PubMed] [Google Scholar]
  18. Prellner K. Complement in pneumococcal infections with varying degrees of severity. Scand J Infect Dis. 1981;13(4):263–268. doi: 10.3109/inf.1981.13.issue-4.04. [DOI] [PubMed] [Google Scholar]
  19. Reed W. P., Davidson M. S., Williams R. C., Jr Complement system in pneumococcal infections. Infect Immun. 1976 Apr;13(4):1120–1125. doi: 10.1128/iai.13.4.1120-1125.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rytel M. W., Dee T. H., Ferstenfeld J. E., Hensley G. T. Possible pathogenetic role of capsular antigens in fulminant pneumococcal disease with disseminated intravascular coagulation (DIC). Am J Med. 1974 Dec;57(6):889–896. doi: 10.1016/0002-9343(74)90166-1. [DOI] [PubMed] [Google Scholar]
  21. Stephens C. G., Williams R. C., Jr, Reed W. P. Classical and alternative complement pathway activation by pneumococci. Infect Immun. 1977 Aug;17(2):296–302. doi: 10.1128/iai.17.2.296-302.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Volanakis J. E., Kaplan M. H. Interaction of C-reactive protein complexes with the complement system. II. Consumption of guinea pig complement by CRP complexes: requirement for human C1q. J Immunol. 1974 Jul;113(1):9–17. [PubMed] [Google Scholar]
  23. Winkelstein J. A., Abramovitz A. S., Tomasz A. Activation of C3 via the alternative complement pathway results in fixation of C3b to the pneumococcal cell wall. J Immunol. 1980 May;124(5):2502–2506. [PubMed] [Google Scholar]
  24. Winkelstein J. A., Bocchini J. A., Jr, Schiffman G. The role of the capsular polysaccharide in the activation of the alternative pathway by the pneumococcus. J Immunol. 1976 Feb;116(2):367–370. [PubMed] [Google Scholar]
  25. Winkelstein J. A., Shin H. S. The role of immunoglobulin in the interaction of pneumococci and the properdin pathway: evidence for its specificity and lack of requirement for the Fc portion of the molecule. J Immunol. 1974 May;112(5):1635–1642. [PubMed] [Google Scholar]
  26. Winkelstein J. A., Shin H. S., Wood W. B., Jr Heat labile opsonins to Pneumococcus. 3. The participation of immunoglobulin and of the alternate pathway of C3 activation. J Immunol. 1972 Jun;108(6):1681–1689. [PubMed] [Google Scholar]
  27. Winkelstein J. A. The role of complement in the host's defense against Streptococcus pneumoniae. Rev Infect Dis. 1981 Mar-Apr;3(2):289–298. doi: 10.1093/clinids/3.2.289. [DOI] [PubMed] [Google Scholar]
  28. Winkelstein J. A., Tomasz A. Activation of the alternative complement pathway by pneumococcal cell wall teichoic acid. J Immunol. 1978 Jan;120(1):174–178. [PubMed] [Google Scholar]
  29. Winkelstein J. A., Tomasz A. Activation of the alternative pathway by pneumococcal cell walls. J Immunol. 1977 Feb;118(2):451–454. [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES