Alternatively spliced CS-1 fibronectin isoform and its receptor VLA-4 in rheumatoid arthritis synovium

J Rheumatol. 1997 Oct;24(10):1873-80.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Allergic Agents / metabolism*
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Arthritis, Rheumatoid / metabolism*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Integrin alpha4beta1
  • Integrins / metabolism*
  • Macrophages / metabolism
  • Male
  • Oligopeptides / metabolism*
  • Osteoarthritis / metabolism
  • RNA, Messenger / analysis
  • Receptors, Lymphocyte Homing / metabolism*
  • Synovial Membrane / blood supply
  • Synovial Membrane / metabolism*


  • Anti-Allergic Agents
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Carrier Proteins
  • Integrin alpha4beta1
  • Integrins
  • Oligopeptides
  • RNA, Messenger
  • Receptors, Lymphocyte Homing
  • glutamyl-isoleucyl-leucyl-aspartyl-valine