HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Szalai, A. J. Articles by Barnum, S. R. Search for Related Content PubMed PubMed Citation Articles by Szalai, A. J. Articles by Barnum, S. R. Pubmed/NCBI databases Substance via MeSH

Experimental Allergic Encephalomyelitis Is Inhibited in Transgenic Mice Expressing Human C-Reactive Protein¹

Alexander J. Szalai^2,*, Serge Nataf, Xian-Zhen Hu^* and Scott R. Barnum^*,

^* Division of Clinical Immunology and Rheumatology, Department of Medicine, and Department of Microbiology, University of Alabama, Birmingham, AL 35294

We show here using a transgenic model that human C-reactive protein (CRP) protects against experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. In transgenic compared with wild-type females, the duration of the human CRP acute phase response that accompanies the inductive phase of active EAE correlates with a delay in disease onset. In transgenic males, which have higher human CRP expression than females do, EAE is delayed, and its severity is reduced relative to same-sex controls. Furthermore, in male transgenics, there is little or no infiltration of the spinal cord by CD3⁺ T cells and CD11b⁺ monocytes and macrophages, and EAE is sometimes prevented altogether. CRP transgenics also resist EAE induced passively by transfer of encephalitogenic T cells from wild-type donors. Human CRP has three effects on cultured encephalitogenic cells that could contribute to the protective effect observed in vivo: 1) CRP inhibits encephalitogenic peptide-induced proliferation of T cells; 2) CRP inhibits production of inflammatory cytokines (TNF-, IFN-) and chemokines (macrophage-inflammatory protein-1, RANTES, monocyte chemoattractant protein-1); and 3) CRP increases IL-10 production. All three of these actions are realized in vitro only in the presence of high concentrations of human CRP. The combined data suggest that during the acute phase of inflammation accompanying EAE, the high level of circulating human CRP that is achieved in CRP-transgenic mice inhibits the damaging action of inflammatory cells and/or T cells that otherwise support onset and development of EAE.

This article has been cited by other articles:

				J. C. Edberg, J. Wu, C. D. Langefeld, E. E. Brown, M. C. Marion, G. McGwin Jr, M. Petri, R. Ramsey-Goldman, J. D. Reveille, S. G. Frank, et al. Genetic variation in the CRP promoter: association with systemic lupus erythematosus Hum. Mol. Genet., April 15, 2008; 17(8): 1147 - 1155. [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]

				D. C. Bullard, X. Hu, J. E. Adams, T. R. Schoeb, and S. R. Barnum p150/95 (CD11c/CD18) Expression Is Required for the Development of Experimental Autoimmune Encephalomyelitis Am. J. Pathol., June 1, 2007; 170(6): 2001 - 2008. [Abstract] [Full Text] [PDF]

				C. Alberda, L. Gramlich, J. Meddings, C. Field, L. McCargar, D. Kutsogiannis, R. Fedorak, and K. Madsen Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial Am. J. Clinical Nutrition, March 1, 2007; 85(3): 816 - 823. [Abstract] [Full Text] [PDF]

				D. C. Bullard, X. Hu, T. R. Schoeb, R. G. Collins, A. L. Beaudet, and S. R. Barnum Intercellular Adhesion Molecule-1 Expression Is Required on Multiple Cell Types for the Development of Experimental Autoimmune Encephalomyelitis J. Immunol., January 15, 2007; 178(2): 851 - 857. [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]

				C. Mold and T. W. Du Clos C-Reactive Protein Increases Cytokine Responses to Streptococcus pneumoniae through Interactions with Fc{gamma} Receptors. J. Immunol., June 15, 2006; 176(12): 7598 - 7604. [Abstract] [Full Text] [PDF]

				P. Baruah, A. Propato, I. E. Dumitriu, P. Rovere-Querini, V. Russo, R. Fontana, D. Accapezzato, G. Peri, A. Mantovani, V. Barnaba, et al. The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens Blood, January 1, 2006; 107(1): 151 - 158. [Abstract] [Full Text] [PDF]

				D. C. Bullard, X. Hu, T. R. Schoeb, R. C. Axtell, C. Raman, and S. R. Barnum Critical Requirement of CD11b (Mac-1) on T Cells and Accessory Cells for Development of Experimental Autoimmune Encephalomyelitis J. Immunol., November 15, 2005; 175(10): 6327 - 6333. [Abstract] [Full Text] [PDF]

				S. Black, I. Kushner, and D. Samols C-reactive Protein J. Biol. Chem., November 19, 2004; 279(47): 48487 - 48490. [Abstract] [Full Text] [PDF]

				R. C. Axtell, M. S. Webb, S. R. Barnum, and C. Raman Cutting Edge: Critical Role for CD5 in Experimental Autoimmune Encephalomyelitis: Inhibition of Engagement Reverses Disease in Mice J. Immunol., September 1, 2004; 173(5): 2928 - 2932. [Abstract] [Full Text] [PDF]

				C. Mold, W. Rodriguez, B. Rodic-Polic, and T. W. Du Clos C-Reactive Protein Mediates Protection from Lipopolysaccharide Through Interactions With Fc{gamma}R J. Immunol., December 15, 2002; 169(12): 7019 - 7025. [Abstract] [Full Text] [PDF]