| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pharmacology and
Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614
C-reactive protein (CRP) is not an acute-phase protein in mice, and therefore, mice are widely used to investigate the functions of human CRP. It has been shown that CRP protects mice from pneumococcal infection, and an active complement system is required for full protection. In this study, we assessed the contribution of CRP’s ability of activating the classical pathway of complement in the protection of mice from lethal infection with virulent Streptococcus pneumoniae type 3. We used two CRP mutants, Y175A and K114A. The Y175A CRP does not bind C1q and does not activate complement in human serum. The K114A CRP binds C1q and activates complement more efficiently than wild-type CRP. Passively administered, both CRP mutants and the wild-type CRP protected mice from infection equally. Infected mice injected with wild-type or mutant CRP had reduced bacteremia, resulting in lower mortality and increased longevity compared with mice that did not receive CRP. Thus, the protection of mice was independent of CRP-mediated activation of the classical pathway of complement. To confirm that human CRP does not differentiate between human and mouse complement, we analyzed the binding of human CRP to mouse C1q. Surprisingly, CRP did not react with mouse C1q, although both mutant and wild-type CRP activated mouse C3, indicating species specificity of CRP-C1q interaction. We conclude that the mouse is an unfit animal for exploring CRP-mediated activation of the classical complement pathway, and that the characteristic of CRP to activate the classical complement pathway has no role in protecting mice from infection.
This article has been cited by other articles:
|
|
 |
|
  M. Salio, S. Chimenti, N. De Angelis, F. Molla, V. Maina, M. Nebuloni, F. Pasqualini, R. Latini, C. Garlanda, and A. Mantovani Cardioprotective Function of the Long Pentraxin PTX3 in Acute Myocardial Infarction Circulation, February 26, 2008; 117(8): 1055 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Deutsch and B. Krishnamoorthy Four-Body Scoring Function for Mutagenesis Bioinformatics, November 15, 2007; 23(22): 3009 - 3015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Ku, H. von Bernuth, C. Picard, S.-Y. Zhang, H.-H. Chang, K. Yang, M. Chrabieh, A. C. Issekutz, C. K. Cunningham, J. Gallin, et al. Selective predisposition to bacterial infections in IRAK-4 deficient children: IRAK-4 dependent TLRs are otherwise redundant in protective immunity J. Exp. Med., October 1, 2007; 204(10): 2407 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Thomas-Rudolph, T. W. Du Clos, C. M. Snapper, and C. Mold C-Reactive Protein Enhances Immunity to Streptococcus pneumoniae by Targeting Uptake to Fc{gamma}R on Dendritic Cells J. Immunol., June 1, 2007; 178(11): 7283 - 7291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Singh, B. Voleti, and A. Agrawal A Novel RBP-J{kappa}-Dependent Switch from C/EBPbeta to C/EBP{zeta} at the C/EBP Binding Site on the C-Reactive Protein Promoter J. Immunol., June 1, 2007; 178(11): 7302 - 7309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Suresh, S. K. Singh, D. A. Ferguson Jr., and A. Agrawal Human C-Reactive Protein Protects Mice from Streptococcus pneumoniae Infection without Binding to Pneumococcal C-Polysaccharide J. Immunol., January 15, 2007; 178(2): 1158 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Rodriguez, C. Mold, M. Kataranovski, J. A. Hutt, L. L. Marnell, J. S. Verbeek, and T. W. Du Clos C-Reactive Protein-Mediated Suppression of Nephrotoxic Nephritis: Role of Macrophages, Complement, and Fc{gamma} Receptors J. Immunol., January 1, 2007; 178(1): 530 - 538. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
