THE ROLE OF ADHESION MOLECULES IN THE PATHOGENESIS OF RHEUMATOID-ARTHRITIS

Rheumatoid arthritis (RA) is a chronic inflammatory disease characteri zed by infiltration of mononuclear cells, mainly T lymphocytes, into t he synovial membrane (SM). The interaction of peripheral blood T cells with the different components of the rheumatoid synovium is mediated by cell surface proteins such as selectins, integrins, members of the immunoglobulin superfamily and homing receptors. T lymphocytes infiltr ating the rheumatoid SM show an activated phenotype and display an inc reased avidity of their adhesion receptors that results in an enhanced interaction of these cells with both extracellular matrix proteins (E CM) and cellular ligands (VCAM-1, ICAMs). The interaction of T cell in tegrins with their ligands, besides an additional antigenic stimulus, could trigger a mitogenic response on these cells, a phenomenon that c an contribute to increased cellularity observed into the rheumatoid SM . Moreover, cell attachment to ECM through integrins induces the secre tion of several proteases that can contribute to the tissue damage obs erved in RA. The increased knowledge about the role of adhesion recept ors in the pathogenesis of RA and other inflammatory diseases will all ow the introduction of a new therapeutic approach by: the use of speci fic blocking reagents designed to interfere with the function of adhes ion molecules.