Vascular cell adhesion molecule-1 (VCAM-1) blockade in collagen-induced arthritis reduces joint involvement and alters B cell trafficking
- Author(s)
- Carter, RA; Campbell, IK; O'Donnell, K; Wicks, IP;
- Details
- Publication Year 2002-04,Volume 128,Issue #1,Page 44-51
- Journal Title
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Vascular cell adhesion molecule-1 (VCAM-1 or CD106) is important in leucocyte trafficking and its increased expression is associated with a number of chronic inflammatory diseases, including rheumatoid arthritis (RA). We used a neutralizing monoclonal antibody (M/K-2-7) to investigate the role of VCAM-1 in collagen-induced arthritis (CIA), an autoimmune model of RA. A single injection of M/K-2.7 (0.5 mg) into naive mice caused leucocytosis within 20 h, due to increased numbers of circulating B cells and macrophages, as well as neutrophils. The most marked effect was on the numbers of immature B cells (B220(lo)IgM+) which were increased approximately fourfold. CIA was elicited in DBA/1 mice by immunization with chick type II collagen (CII) in Freund's complete adjuvant, followed by a repeat injection 21 days later. Repeated M/K-2-7 administration from the time of primary CII immunization reduced the clinical severity, but not the incidence, of CIA compared to isotype-control monoclonal antibody-treated mice. Histological assessment showed fewer arthritic joints in M/K-2.7-treated mice; however, affected joints showed the same range of severity as those of control mice. Anti-CII IgG1 levels were reduced in anti-VCAM-1-treated mice but the cellular immune response to CII was unaffected. In contrast, VCAM-1 blockade from the onset of clinical features of CIA did not prevent disease progression. These results establish a role for VCAM-1 in promoting polyarticular involvement in CIA, most probably via an effect on B cells.
- Publisher
- BLACKWELL PUBLISHING LTD
- Keywords
- FIBROBLAST-LIKE SYNOVIOCYTES; FOLLICULAR DENDRITIC CELLS; RHEUMATOID-ARTHRITIS; BONE-MARROW; INFLAMMATORY ARTHRITIS; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; DEFICIENT MICE; INTEGRIN VLA-4; SYNOVIAL-FLUID
- Publisher's Version
- https://doi.org/10.1046/j.1365-2249.2002.01794.x
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- Refer to copyright notice on published article.
Creation Date: 2002-04-01 12:00:00