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The Inhibitory Co-Receptor, PECAM-1 Provides a Protective Effect in Suppression of Collagen-Induced Arthritis

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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.

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Authors and Affiliations

  1. Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia

    MAE-XHUM WONG, P. Mark Hogarth & Denise E. Jackson

  2. Dame Roma Mitchell Cancer Research Laboratories, Hanson Institute, IMVS, Adelaide, South Australia

    John D. Hayball

  3. Kronheimer Building, Austin Research Institute, Austin Hospital, Studley Road, Heidelberg, Victoria, 3084, Australia

    Denise E. Jackson

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  1. MAE-XHUM WONG
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  2. John D. Hayball
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  3. P. Mark Hogarth
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  4. Denise E. Jackson
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Correspondence to Denise E. Jackson.

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WONG, MX., Hayball, J.D., Hogarth, P.M. et al. The Inhibitory Co-Receptor, PECAM-1 Provides a Protective Effect in Suppression of Collagen-Induced Arthritis. J Clin Immunol 25, 19–28 (2005). https://doi.org/10.1007/s10875-005-0354-7

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  • DOI: https://doi.org/10.1007/s10875-005-0354-7

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