Abstract
Expression of a human C-reactive protein (CRP) transgene has been shown to protect mice from lethal Streptococcus pneumoniae infection. In the present study, we used cobra venom factor-induced decomplementation to investigate the role of complement in this CRP-mediated protection. An intact complement system significantly reduced pneumococcal bacteremia at 24 h postinfection and extended median survival time of both CRP-transgenic and nontransgenic mice. However, mortality was significantly lowered only for CRP transgenic mice. The transgene significantly reduced bacteremia for both normocomplementemic and decomplemented mice, but it resulted in a significantly longer median survival time and lower mortality only for normocomplementemic mice. These data suggest that in vivo complement and CRP amplify each other's protective capacity, particularly during the early course of infection.
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- Ciliberto G., Arcone R., Wagner E. F., Rüther U. Inducible and tissue-specific expression of human C-reactive protein in transgenic mice. EMBO J. 1987 Dec 20;6(13):4017–4022. doi: 10.1002/j.1460-2075.1987.tb02745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ganrot P. O., Kindmark C. O. C-reactive protein--a phagocytosis-promoting factor. Scand J Clin Lab Invest. 1969 Oct;24(3):215–219. doi: 10.3109/00365516909080155. [DOI] [PubMed] [Google Scholar]
- Guyre P. M., Campbell A. S., Kniffin W. D., Fanger M. W. Monocytes and polymorphonuclear neutrophils of patients with streptococcal pharyngitis express increased numbers of type I IgG Fc receptors. J Clin Invest. 1990 Dec;86(6):1892–1896. doi: 10.1172/JCI114921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horowitz J., Volanakis J. E., Briles D. E. Blood clearance of Streptococcus pneumoniae by C-reactive protein. J Immunol. 1987 Apr 15;138(8):2598–2603. [PubMed] [Google Scholar]
- Hosea S. W., Brown E. J., Frank M. M. The critical role of complement in experimental pneumococcal sepsis. J Infect Dis. 1980 Dec;142(6):903–909. doi: 10.1093/infdis/142.6.903. [DOI] [PubMed] [Google Scholar]
- Kilpatrick J. M., Volanakis J. E. Opsonic properties of C-reactive protein. Stimulation by phorbol myristate acetate enables human neutrophils to phagocytize C-reactive protein-coated cells. J Immunol. 1985 May;134(5):3364–3370. [PubMed] [Google Scholar]
- Kindmark C. O. Stimulating effect of C-reactive protein on phagocytosis of various species of pathogenic bacteria. Clin Exp Immunol. 1971 Jun;8(6):941–948. [PMC free article] [PubMed] [Google Scholar]
- Le P. T., Muller M. T., Mortensen R. F. Acute phase reactants of mice. I. Isolation of serum amyloid P-component (SAP) and its induction by a monokine. J Immunol. 1982 Aug;129(2):665–672. [PubMed] [Google Scholar]
- Marnell L. L., Mold C., Volzer M. A., Burlingame R. W., Du Clos T. W. C-reactive protein binds to Fc gamma RI in transfected COS cells. J Immunol. 1995 Aug 15;155(4):2185–2193. [PubMed] [Google Scholar]
- Mold C., Nakayama S., Holzer T. J., Gewurz H., Du Clos T. W. C-reactive protein is protective against Streptococcus pneumoniae infection in mice. J Exp Med. 1981 Nov 1;154(5):1703–1708. doi: 10.1084/jem.154.5.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakayama S., Gewurz H., Holzer T., Du Clos T. W., Mold C. The role of the spleen in the protective effect of C-reactive protein in Streptococcus pneumoniae infection. Clin Exp Immunol. 1983 Nov;54(2):319–326. [PMC free article] [PubMed] [Google Scholar]
- Nunomura W., Takakuwa Y., Higashi T. Changes in serum concentration and mRNA level of rat C-reactive protein. Biochim Biophys Acta. 1994 Oct 21;1227(1-2):74–78. doi: 10.1016/0925-4439(94)90109-0. [DOI] [PubMed] [Google Scholar]
- Richardson M. D., Gray C. A., Shankland G. S. Opsonic effect of C-reactive protein on phagocytosis and intracellular killing of virulent and attenuated strains of Candida albicans by human neutrophils. FEMS Microbiol Immunol. 1991 Nov;3(6):341–344. doi: 10.1111/j.1574-6968.1991.tb04259.x. [DOI] [PubMed] [Google Scholar]
- Richardson M. D., Shankland G. S., Gray C. A. Opsonizing activity of C-reactive protein in phagocytosis of Aspergillus fumigatus conidia by human neutrophils. Mycoses. 1991 Mar-Apr;34(3-4):141–143. doi: 10.1111/j.1439-0507.1991.tb00635.x. [DOI] [PubMed] [Google Scholar]
- Szalai A. J., Briles D. E., Volanakis J. E. Human C-reactive protein is protective against fatal Streptococcus pneumoniae infection in transgenic mice. J Immunol. 1995 Sep 1;155(5):2557–2563. [PubMed] [Google Scholar]
- Taktak Y. S., Stenning B. Solid phase enzyme immunoassays for the quantification of serum amyloid P (SAP) and complement component 3 (C3) proteins in acute-phase mouse sera. Horm Metab Res. 1992 Aug;24(8):371–374. doi: 10.1055/s-2007-1003338. [DOI] [PubMed] [Google Scholar]
- Tebo J. M., Mortensen R. F. Characterization and isolation of a C-reactive protein receptor from the human monocytic cell line U-937. J Immunol. 1990 Jan 1;144(1):231–238. [PubMed] [Google Scholar]
- Till G. O., Morganroth M. L., Kunkel R., Ward P. A. Activation of C5 by cobra venom factor is required in neutrophil-mediated lung injury in the rat. Am J Pathol. 1987 Oct;129(1):44–53. [PMC free article] [PubMed] [Google Scholar]
- Van den Berg C. W., Aerts P. C., Van Dijk H. In vivo anti-complementary activities of the cobra venom factors from Naja naja and Naja haje. J Immunol Methods. 1991 Feb 15;136(2):287–294. doi: 10.1016/0022-1759(91)90015-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Yother J., Volanakis J. E., Briles D. E. Human C-reactive protein is protective against fatal Streptococcus pneumoniae infection in mice. J Immunol. 1982 May;128(5):2374–2376. [PubMed] [Google Scholar]