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Type: Journal article
Title: The inhibitory co-receptor, PECAM-1 provides a protective effect in suppression of collagen-induced arthritis
Author: Wong, M.
Hayball, J.
Hogarth, P.
Jackson, D.
Citation: Journal of Clinical Immunology, 2005; 25(1):19-28
Publisher: Kluwer Academic/plenum Publ
Issue Date: 2005
ISSN: 0271-9142
Statement of
Mae-Xhum Wong, John D. Hayball, P. Mark Hogarth, Denise E. Jackson
Abstract: Studies of PECAM-1(-/-) mice have identified that PECAM-1 functions as an inhibitory co-receptor to modulate immunological responsiveness. In this study, we describe the in vivo consequences of PECAM-1 deficiency in mouse models of collagen-induced arthritis (CIA) and K/BxN passive transfer model that resembles many of the features of human rheumatoid arthritis. Immunization of PECAM-1(-/-) C57BL/6 (H-2b) mice with chicken collagen type II induced CIA with an incidence of 82% by day 49, while 33%; of wild-type and 100% of DBA/1 mice developed arthritis in a similar time frame. The mean onset of disease for PECAM-1(-/-) C57BL/6 mice was day 32 compared to day 51 for wild-type C57BL/6 mice and day 18 for DBA/1 mice (H-2q susceptible). In terms of disease severity, the mean maximal arthritic index for PECAM-1(-/-) C57BL/6 mice was comparable to DBA/1 mice (8.91 +/- 0.91 vs 11.67 +/- 0.82). This mean maximal index in PECAM-1(-/-) C57BL/6 mice was significantly higher than wild-type C57BL/6 mice (5.00 +/- 0.73). IgG1 and IgG2b antibody responses against CII were elevated in arthritic PECAM-1(-/-) C57BL/6 mice compared to wild-type C57BL/6 mice. Histological examination of arthritic paws of PECAM-1(-/-) C57BL/6 mice revealed inflammatory infiltrates of lymphocytic/monocytic cells and cartilage/bone destruction similar to CIA-induced DBA/1 arthritic paws. In the K/BxN model, the arthritis was not augmented in PECAM-1(-/-) mice compared to wild-type mice. In contrast, in active CIA, PECAM-1(-/-) mice developed severe disease comparable to susceptible DBA/1 mice and profoundly more severe than C57BL/6 mice, where only one third developed a mild/moderate disease. Together these observations suggest that PECAM-1 plays a crucial role in the suppression of development of autoimmune arthritis.
Keywords: Cartilage
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Arthritis, Experimental
Arthritis, Rheumatoid
Disease Models, Animal
Collagen Type II
Adoptive Transfer
Platelet Endothelial Cell Adhesion Molecule-1
DOI: 10.1007/s10875-005-0354-7
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