| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425;
Institute of Disease Control and Prevention, Academy of Military Medical Science, Beijing, China; and
Departments of Medicine and Immunology, Division of Rheumatology, University of Colorado Health Sciences Center, Aurora, CO 80045
Collagen-induced arthritis (CIA) represents an animal model of autoimmune polyarthritis with similarities to human rheumatoid arthritis, and therapy with various systemic complement-inhibitory proteins has been investigated in this model with varying results. We investigated the use of complement receptor 2 (CR2)-Crry, a complement inhibitor with the ability to target C3 breakdown products deposited in a rheumatic joint. Following induction of CIA in DBA/1J mice, animals were treated with either PBS or CR2-Crry (every other day, every 4 days, or with a single injection). The severity of clinical disease was significantly reduced in all CR2-Crry-treated groups compared with controls. Joints from mice receiving multiple doses of CR2-Crry showed significantly decreased inflammatory cell infiltrate, cartilage damage, pannus formation, and bone damage. CR2-Crry treatment also significantly decreased production of anti-collagen IgG and the inflammatory cytokines TNF-
and IL-1β. IL-10 and IL-1Ra levels were increased in CR2-Crry-treated mice. CR2-Crry localized preferentially in the joints of mice with CIA. Analysis of IgG and C3 deposition in the joints of treated animals indicated that both complement regulation and the modulation of anti-collagen Ab production contributed to the protective effects of CR2-Crry. Of interest, a previous study reported that Crry-Ig, an untargeted counterpart of CR2-Crry, had minimal effect on disease, even when administered at a sufficiently high dose to maintain chronic complement inhibition.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a fellowship from the Arthritis Foundation (to H.S.) and grants from the Alliance for Lupus Research (to S.T.), National Institutes of Health R01 AR51749 (to V.M.H.), and National Institutes of Health Grant C06 RR015455 for construction and upgrade of animal facilities.
2 H.S. and F.Q. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Stephen Tomlinson, Department of Microbiology and Immunology, Children’s Research Institute, Medical University of South Carolina, Charleston, SC 29425. E-mail address: tomlinss{at}musc.edu
4 Abbreviations used in this paper: RA, rheumatoid arthritis; CIA, collagen-induced arthritis; CII, bovine type II collagen; CR1, complement receptor 1; CR2, complement receptor 2; VCP, vaccinia virus complement control protein.
This article has been cited by other articles:
|
|
 |
|
  N. K. Banda, B. Levitt, M. J. Glogowska, J. M. Thurman, K. Takahashi, G. L. Stahl, S. Tomlinson, W. P. Arend, and V. M. Holers Targeted Inhibition of the Complement Alternative Pathway with Complement Receptor 2 and Factor H Attenuates Collagen Antibody-Induced Arthritis in Mice J. Immunol., November 1, 2009; 183(9): 5928 - 5937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Lappegard, D. Christiansen, A. Pharo, E. B. Thorgersen, B. C. Hellerud, J. Lindstad, E. W. Nielsen, G. Bergseth, D. Fadnes, T. G. Abrahamsen, et al. Human genetic deficiencies reveal the roles of complement in the inflammatory network: Lessons from nature PNAS, September 15, 2009; 106(37): 15861 - 15866. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
