Vascular cell adhesion molecule-1 (VCAM-1) blockade in collagen-induced arthritis reduces joint involvement and alters B cell trafficking.
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 (B220loIgM+) 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.
Carter
R A
RA
Reid Rheumatology Laboratory, Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Campbell
I K
IK
O'Donnel
K L
KL
Wicks
I P
IP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D018450:Disease Progression; D007074:Immunoglobulin G / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000473:pathology; D007964:Leukocytosis / Q000209:etiology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D007074:Immunoglobulin G; D019010:Vascular Cell Adhesion Molecule-1