Alternatively spliced CS-1 fibronectin isoform and its receptor VLA-4 in rheumatoid arthritis synovium.
OBJECTIVE
Extracellular matrix components and cell adhesion molecules play a role in the pathogenesis of rheumatoid arthritis (RA). Interaction between the integrin very late antigen-4 (VLA-4) and the connecting segment-1 (CS-1) fibronectin (FN) isoform may contribute to lymphocyte interaction in RA synovium. We examined both mRNA and protein expression of CS-1 FN in inflamed synovium, and VLA-4 expression in synovial tissue and on cultured fibroblast-like synoviocytes from patients with RA.


METHODS
Snap frozen synovial tissue specimens of 10 patients with RA and 4 patients with osteoarthritis were examined for expression of CS-1 FN mRNA and protein by in situ hybridization and immunohistochemistry. VLA-4 expression of synovial fibroblasts and in synovial tissue was evaluated by flow cytometry and immunohistochemistry.


RESULTS
CS-1 FN mRNA was detected in RA lining layer synoviocytes, around terminal vessels, and in endothelial cells. Double labeling revealed that most lining synoviocytes expressing CS-1 FN mRNA were CD68 negative. VLA-4 was found in RA synovial fibroblasts, sublining mononuclear cells, and lymphoid aggregates.


CONCLUSIONS
Our findings suggest that expression of CS-1 FN may partially correlate with cell proliferation in the RA lining layer. VLA-4 was found in RA synovial lining, as well as on cultured synovial fibroblasts. Thus, VLA-4/CS-1 FN interaction may facilitate lymphocyte interaction and synovial proliferation in RA.
Müller-Ladner
U
U
Department of Internal Medicine I, University of Regensburg, Germany.
Elices
M J
MJ
Kriegsmann
J B
JB
Strahl
D
D
Gay
R E
RE
Firestein
G S
GS
Gay
S
S
D018926:Anti-Allergic Agents / Q000378:metabolism*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D013583:Synovial Membrane / Q000098:blood supply / Q000378:metabolism*; D000097382:CD68 Molecule
D018926:Anti-Allergic Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D039041:Integrin alpha4beta1; D016023:Integrins; D009842:Oligopeptides; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C094697:glutamyl-isoleucyl-leucyl-aspartyl-valine