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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1997 Jan;56(1):45–51. doi: 10.1136/ard.56.1.45

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

N Rinaldi 1, M Schwarz-Eywill 1, D Weis 1, P Leppelmann-Jansen 1, M Lukoschek 1, U Keilholz 1, T Barth 1
PMCID: PMC1752256  PMID: 9059141

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.



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Figure 1  .

Figure 1  

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Histograms of flow cytometric analysis for the α1, α5, and β1 integrin subunits on fibroblast-like synoviocytes (FBS) from normal synovium (NS, upper panels) and from rheumatoid arthritis (RA, lower panels). The fluorescence obtained with isotypic negative control antibodies is plotted as a plain line, the results with anti-integrin antibodies as a bold line.

Figure 2  .

Figure 2  

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Adhesion of fibroblast-like synoviocytes (FBS) from normal synovium (NS) and from synovium derived from patients with rheumatoid arthritis (RA). The assays were performed as described in Methods. The diagram shows percent adhesion of the total number of cells plated. Data are reported as the mean of assays of seven normal FBS cultures and seven rheumatoid arthritis FBS cultures. Bars = SD. *P < 0.05 v normal FBS.

Figure 3  .

Figure 3  

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Inhibition of adhesion of fibroblast-like synoviocytes (FBS) from normal synovium (NS) and from rheumatoid arthritis (RA) to the ECM proteins. Monoclonal antibodies (mAb) against α2, α3, α4, α5, α6, β1, and β3 were used; however, only mAb which blocked FBS binding are shown in the figure. Inhibition through the mAb is given as relative percent adhesion compared to adhesion without antibodies (100%). Data represent the means of assays of three normal FBS cultures and of three rheumatoid arthritis FBS cultures. Bars = SD. *P < 0.05 v normal FBS.

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