Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins

Abstract

Objective - To compare in vitro expression of β1, β3, and β4 integrins in normal fibroblast-like synoviocytes (FBS) and in FBS from rheumatoid arthritis (RA) synovium and to investigate the adhesion of normal FBS and RA-FBS to the integrin binding extracellular matrix (ECM) proteins: collagen type IV, fibronectin, laminin, and tenascin. Methods - Expression of integrin receptors of cultured FBS was detected by flow cytometry. Attachment of FBS to ECM proteins was quantified by adhesion assays. Inhibition studies were performed using monoclonal antibodies to the integrin subunits. Results - Compared with normal FBS, RA-FBS showed increased expression of α1 to α6, β1, and β4 integrin subunits and enhanced binding of ECM proteins. Binding to ECM proteins was partly or completely blocked by an anti-β1 integrin antibody and antibodies to α3, α5, and α6 integrin subunits. The blocking efficiency was significantly (P < 0.05) higher in RA-FBS than in normal FBS. Conclusions - The enhanced expression of the β1 integrin receptors on cultured RA-FBS correlated with increased attachment to ECM proteins. Adhesion of normal and RA-FBS to ECM proteins is mediated through β1 integrin receptors. Therefore, the tight binding of rheumatoid FBS to the matrix via β1 integrins might play a role in ECM remodelling in the rheumatoid process in vivo.