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The Journal of Immunology, Vol 157, Issue 1 473-479, Copyright © 1996 by American Association of Immunologists
ARTICLES |
GJ Wolbink, MC Brouwer, S Buysmann, IJ ten Berge and CE Hack
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
The in vivo function of C-reactive protein (CRP) is unknown. Among the in vitro functions assigned to CRP is the ability to activate complement via the classical pathway. To date, there is no evidence supporting that CRP exerts this function in vivo. We here show a novel approach to assess CRP-mediated complement activation in vivo, which is based on the property that activated complement factors C3 and C4 fix to CRP during complement activation induced by this acute phase protein. We developed specific ELISAs for complexes between CRP and C4b, C4d, C3b, or C3d. We established that in vitro complement-CRP complexes were formed only during CRP-dependent activation, and not during activation by other activators, even in the presence of high CRP levels. Circulating levels of complement-CRP complexes were undetectable in normal donors, but significantly increased in nine patients following implantation of a renal allograft. Importantly, levels of complement-CRP complexes did not change in these patients upon a bolus infusion of mAb OKT3, which induces activation of the classical complement pathway, demonstrating in vivo that complement-CRP complexes are not formed during CRP-independent activation of complement, even when CRP is elevated. We conclude that measurement of complement-CRP complexes provides a suitable tool to study CRP-mediated activation of complement in vivo. Furthermore, increased levels of these complexes occur in clinical samples, indicating that CRP may induce activation of complement in vivo.
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P. M. Ridker, M. Cushman, M. J. Stampfer, R. P. Tracy, and C. H. Hennekens Plasma Concentration of C-Reactive Protein and Risk of Developing Peripheral Vascular Disease Circulation, February 10, 1998; 97(5): 425 - 428. [Abstract] [Full Text] [PDF] |
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P. Bruins, H. t. Velthuis, A. P. Yazdanbakhsh, P. G. M. Jansen, F. W. J. van Hardevelt, E. M. F. H. de Beaumont, C. R. H. Wildevuur, L. Eijsman, A. Trouwborst, and C. E. Hack Activation of the Complement System During and After Cardiopulmonary Bypass Surgery : Postsurgery Activation Involves C-Reactive Protein and Is Associated With Postoperative Arrhythmia Circulation, November 18, 1997; 96(10): 3542 - 3548. [Abstract] [Full Text] |
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W. K. Lagrand, H. W.M. Niessen, G.-J. Wolbink, L. H. Jaspars, C. A. Visser, F. W.A. Verheugt, C. J.L.M. Meijer, and C. E. Hack C-Reactive Protein Colocalizes With Complement in Human Hearts During Acute Myocardial Infarction Circulation, January 7, 1997; 95(1): 97 - 103. [Abstract] [Full Text] |
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A. Wakatsuki, Y. Okatani, N. Ikenoue, and T. Fukaya Effect of Medroxyprogesterone Acetate on Vascular Inflammatory Markers in Postmenopausal Women Receiving Estrogen Circulation, March 26, 2002; 105(12): 1436 - 1439. [Abstract] [Full Text] [PDF] |
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