Extended reports
Differential expression and functional behaviour of the
v and
3 integrin subunits in cytokine stimulated fibroblast-like cells
derived from synovial tissue of rheumatoid arthritis and osteoarthritis
in vitro
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
v and
3 subunits in synovial
lining cells (SLC) of chronic synovitis occurring in
osteoarthritis (OA) and in rheumatoid arthritis (RA). The
expression and function of
v and
3 as VN receptor in cultured fibroblast-like synoviocytes (FBS) derived from patients with OA and RA
was also compared.
METHODS
Expression of
v and
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
v and
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 1
(IL1
) and tumour necrosis
factor
(TNF
) 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
v and
3 subunits. OA-SLC strongly and
uniformly expressed
v whereas RA-SLC showed heterogeneous expression
of
v. In situ both OA-SLC and RA-SLC lacked the expression of the
integrin subunit
3. In in vitro studies, OA-FBS and RA-FBS did not
differ as regards expression of
v and
3, and VN attachment.
Binding of RA-FBS to VN was partially blocked by antibodies against
v,
1, and
3 subunits, whereas only antibodies against
v and
3 inhibited the binding of OA-FBS to VN. The proinflammatory
cytokines TNF
and IL1
increased the expression of
v and
3,
and the VN binding of OA-FBS, whereas
v and
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
3 seems to be
one partner but not the major one with which the subunit
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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