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

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). 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-γ (IFNγ) 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. 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. IFNγ 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. 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. [ABSTRACT FROM AUTHOR]