Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1

Arthritis Rheum. 2003 Nov;48(11):3280-90. doi: 10.1002/art.11268.


Objective: Platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) is a member of the immunoglobulin superfamily that is expressed in platelets, leukocytes, and endothelial cells. PECAM-1 has been shown to play a role in transendothelial migration of leukocytes and contains immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail and inhibits cellular responses. We examined the role of PECAM-1 in the development of collagen-induced arthritis (CIA).

Methods: CIA was induced in PECAM-1-deficient DBA/1 mice. The incidence of arthritis and the arthritis index were examined. Anti-type II collagen (anti-CII) antibody levels and interferon-gamma (IFNgamma) production by lymph node cells and spleen cells were determined. Lymphocytes from arthritic PECAM-1-deficient and wild-type mice were labeled with dye, transferred to arthritic PECAM-1(+/-) mice, and cell migration to inflamed joints was examined.

Results: PECAM-1-deficient mice showed accelerated onset of arthritis and increased severity only during the early phase. Anti-CII antibody levels were also increased during the early phase. IFNgamma production by lymph node cells and spleen cells from PECAM-1-deficient mice in response to CII was higher than that in wild-type mice. Lymphocytes from arthritic PECAM-1-deficient mice showed accelerated migration to inflamed joints, but not lymph nodes or spleen. The development of anti-CII antibody-induced arthritis was similar in PECAM-1-deficient and wild-type mice.

Conclusion: These results indicate that PECAM-1 negatively regulates humoral and cell-mediated immune responses and lymphocyte migration into joints and, consequently, the development of CIA. In addition, the role of PECAM-1 in the transendothelial migration of leukocytes appears to be redundant in this model.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Autoantibodies / blood
  • Cell Movement
  • Collagen Type II* / immunology
  • Collagen Type II* / pharmacology
  • Disease Models, Animal
  • Hindlimb / pathology
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Joints / pathology
  • Lymph Nodes / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes / immunology


  • Autoantibodies
  • Collagen Type II
  • Immunoglobulin G
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Interferon-gamma