Journal of Clinical Immunology

, Volume 25, Issue 1, pp 19–28 | Cite as

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

  • John D. Hayball
  • P. Mark Hogarth
  • Denise E. Jackson


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.


Rheumatoid arthritis collagen-induced arthritis PECAM-1 knockout mouse 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

    • 1
  • John D. Hayball
    • 2
  • P. Mark Hogarth
    • 1
  • Denise E. Jackson
    • 1
    • 3
  1. 1.Austin Research InstituteAustin HospitalHeidelbergAustralia
  2. 2.Dame Roma Mitchell Cancer Research LaboratoriesHanson Institute, IMVSAdelaideSouth Australia
  3. 3.Kronheimer Building, Austin Research InstituteAustin HospitalHeidelbergAustralia

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