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Annals of the Rheumatic Diseases 1997;56:729-736; doi:10.1136/ard.56.12.729
Copyright © 1997 BMJ Publishing Group Ltd & European League Against Rheumatism.
Ann Rheum Dis 1997;56:729-736 ( December )

Extended reports

Differential expression and functional behaviour of the alpha v and beta 3 integrin subunits in cytokine stimulated fibroblast-like cells derived from synovial tissue of rheumatoid arthritis and osteoarthritis in vitro Nadia Rinaldi,a D Weis,a B Brado,a M Schwarz-Eywill,b M Lukoschek,c A Pezzutto,d U Keilholz,a T F E Barthe

a Department of Internal Medicine V, University of Heidelberg, Germany, b Department of Internal Medicine I, Friedrichstadt Dresden, Germany, c Department of Orthopaedic Surgery, University of Heidelberg, Germany, d Department of Haematology, Robert-Rössle Klinik, Virchow-Klinikum, University of Berlin, Germany, e Institute of Pathology, University of Ulm, Germany

Correspondence to: Dr T F E Barth, Institute of Pathology, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.

Accepted for publication 18 September 1997

OBJECTIVE---The aim of this study was to investigate in situ the expression of the classic vitronectin (VN) receptor consisting of the alpha v and beta 3 subunits in synovial lining cells (SLC) of chronic synovitis occurring in osteoarthritis (OA) and in rheumatoid arthritis (RA). The expression and function of alpha v and beta 3 as VN receptor in cultured fibroblast-like synoviocytes (FBS) derived from patients with OA and RA was also compared.
METHODS---Expression of alpha v and beta 3 was examined immunohistochemically in normal synovial tissue and in synovial tisssue from patients with OA and RA. The effect of proinflammatory cytokines and of a synovial fluid of a patient with RA on the expression of the alpha v and beta 3 subunits of cultured FBS was determined by flow cytometry. Binding of OA and RA-FBS to VN was quantified using adhesion assays and the effect of interleukin 1beta (IL1beta ) and tumour necrosis factor alpha  (TNFalpha ) on adhesion was measured. The specifity of the adhesion was tested by inhibition studies using monoclonal antibodies to integrin subunits.
RESULTS---In in situ studies normal SLC showed a parallel distribution of alpha v and beta 3 subunits. OA-SLC strongly and uniformly expressed alpha v whereas RA-SLC showed heterogeneous expression of alpha v. In situ both OA-SLC and RA-SLC lacked the expression of the integrin subunit beta 3. In in vitro studies, OA-FBS and RA-FBS did not differ as regards expression of alpha v and beta 3, and VN attachment. Binding of RA-FBS to VN was partially blocked by antibodies against alpha v, beta 1, and beta 3 subunits, whereas only antibodies against alpha v and beta 3 inhibited the binding of OA-FBS to VN. The proinflammatory cytokines TNFalpha and IL1beta increased the expression of alpha v and beta 3, and the VN binding of OA-FBS, whereas alpha v and beta 3 expression, and VN binding were downregulated in RA-FBS. Similar effects were found when the synovial fluid of an RA patient was used.
CONCLUSION---The integrin subunit beta 3 seems to be one partner but not the major one with which the subunit alpha v forms functional vitronectin receptors in OA-FBS and RA-FBS. The interaction between synovial cells and inflammatory cytokines seems to be different for OA and RA; the basis for this difference, however, remains to be established.


© 1997 by Annals of the Rheumatic Diseases

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