DIFFERENTIAL EXPRESSION AND FUNCTIONAL-BEHAVIOR 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

Objective-The aim of this study was to investigate in situ the express ion of the classic vitronectin (VN) receptor consisting of the alpha v and beta 3 subunits in synovial lining cells (SLC) of chronic synovit is occurring in osteoarthritis (OA) and in rheumatoid arthritis (RA). The expression and function of alpha v and beta 3 as VN receptor in cu ltured fibroblast-like synoviocytes (FBS) derived from patients with O A and RA was also compared. Methods-Expression of alpha v and beta 3 w as examined immunohistochemically in normal synovial tissue and in syn ovial tisssue from patients with OA and RA. The effect of proinflammat ory cytokines and of a synovial fluid of a patient with RA on the expr ession of the alpha v and beta 3 subunits of cultured FBS was determin ed by flow cytometry. Binding of OA and RA-FBS to VN was quantified us ing adhesion assays and the effect of interleukin 1 beta (IL1 beta) an d tumour necrosis factor alpha (TNF alpha) on adhesion was measured. T he specifity of the adhesion was tested by inhibition studies using mo noclonal antibodies to integrin subunits. Results-In in situ studies n ormal SLC showed a parallel distribution of alpha v and beta 3 subunit s. OA-SLC strongly and uniformly expressed alpha v whereas RA-SLC show ed 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 stu dies, 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, w hereas only antibodies against alpha v and beta 3 inhibited the bindin g of OA-FBS to VN. The proinflammatory cytokines TNF alpha and IL1 bet a increased the expression of alpha v and beta 3, and the VN binding o f OA-FBS, whereas alpha v and beta 3 expression, and VN binding were d ownregulated in RA-FBS. Similar effects were found when the synovial f luid 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. T he 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.