Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1)/CD106 have been reported in synovial fluid (SF) from patients with rheumatoid arthritis (RA). In the present study, VCAM-1-positive lymphocytes were found in SF from RA patients. The data strongly suggest that sVCAM-1 might be bound to lymphocytes in SF. rsVCAM-1 in the fluid phase can bind to both SF lymphocytes and IL-2-dependent T cell lines with up-regulated expression and binding activity of VLA-4. Furthermore, proliferative responses of SF mononuclear cells (SFMC) with PHA, immobilized anti-CD3, or anti-CD2 and PMA were inhibited to various extents in the presence of rsVCAM-1, but only PMA-induced proliferative response of PBMC from normal individuals was inhibited notably in the presence of rsVCAM-1. rsVCAM-1 also drastically reduced IL-2 production of Jurkat leukemic T cells possessing high affinity VLA-4 with the stimulation of anti-CD3 and PMA, suggesting that the T cell hyporesponsiveness induced by rsVCAM-1 might stem from impairment of IL-2 production. These results indicate that sVCAM-1 provides a negative signal to T cell activation, probably by affecting the pathway of protein kinase C activation. Thus, binding of sVCAM-1 to SF lymphocytes might partly explain the anergic state of these lymphocytes.

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