EXPRESSION OF CD44 VARIANTS IN HUMAN INFLAMMATORY SYNOVITIS

The cell surface hyaluronate receptor CD44 has previously been shown t o have immunomodulatory activity and to be upregulated in inflammatory synovitis. Since these findings were reported, the genomic structure of CD44 has been delineated, and multiple splice variants have been de scribed. Therefore, we determined which CD44 variant exons are present during inflammatory synovitis by a combination of northern blot analy sis and reverse transcription followed by polymerase chain reaction am plification of synovial RNA. Immunohistochemical staining was used to define the sites of expression of individual v6 and v9 exons in synovi al tissue. The standard (S) or hematopoietic isoform, CD44S, was the p redominant form of CD44 expressed in synovium and was expressed by mos t cell types. Other isoforms, containing alternatively spliced exons i n the proximal extracellular domain, were found by RT-PCR, but at lowe r levels than CD44S. The second most prevalent form was CD44E, which h as an insertion of three exons (v8-v10) in the proximal extracellular domain. Immunohistochemical studies showed that reactivity with v9-spe cific antibodies was primarily in macrophages, particularly those in t he synovial lining layer. CD44 exon v6, previously reported to be impo rtant in immune activation and in epithelial tumor metastasis, was als o expressed in synovial lining cells and in occasional synovial inters titial cells. The presence of CD44 variants containing v9 in rheumatoi d synovial macrophages may be important in the adhesion and activation of mononuclear phagocytes in the synovium and, thus, may be a target for novel antiinflammatory therapies in the future. The role of CD44 i soforms in cellular adhesion, immune activation, and joint erosion in inflammatory synovitis deserves further study.