VASCULAR CELL-ADHESION MOLECULE-1 (CD106) ON PRIMARY HUMAN ARTICULAR CHONDROCYTES - FUNCTIONAL REGULATION OF EXPRESSION BY CYTOKINES AND COMPARISON WITH INTERCELLULAR-ADHESION MOLECULE-1 (CD54) AND VERY LATE ACTIVATION ANTIGEN-2

Objective. To investigate the expression of adhesion molecules belongi ng to the immunoglobulin superfamily on human primary articular chondr ocytes and to determine their response pattern to cytokines with respe ct to the adhesion of lymphocytes. Methods. The expression of adhesion molecules was studied by flow cytometry (cultured cells), immunohisto chemistry (cartilage), reverse transcription-polymerase chain reaction , and Northern blotting. Adhesion of T cells to chondrocytes was measu red using the Jurkat T cell line. Results. Vascular cell adhesion mole cule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were fo und to be constitutively expressed on large percentages of unstimulate d chondrocytes in culture and in cartilage ex vivo. ICAM-2, ICAM3, and very late activation antigen 4 (VLA-4; alpha 4 beta 1 integrin), the ligand for VCAM-1, were not detected. Interleukin-lp (IL-1 beta) and t umor necrosis factor alpha (TNF alpha) further induced VCAM-1 and ICAM -1 messenger RNA and protein expression. Transforming growth factor be ta (TGF beta) had no effect on ICAM-1 and decreased the expression of VCAM-1, Another adhesion molecule, VLA-2 (alpha 2 beta 1 integrin) tha t was also expressed on unstimulated chondrocytes, was differentially regulated by cytokines, While neither IL-1 beta nor TNF alpha had any effect on expression of VLA2, TGF beta markedly increased the alpha 2 subunit of VLA-2. Adhesion of Jurkat T cells to chondrocytes was furth er induced by IL-1 beta and TNF alpha. Pretreatment of chondrocytes wi th monoclonal antibodies to VCAM-1 and ICAM-1 inhibited adhesion of T cells to chondrocytes. Conclusion. VCAM-1, ICAM-1, and VLA-2 are const itutively expressed by human articular chondrocytes, Expression is reg ulated by cytokines, As shown for other chondrocyte genes, IL-1 beta/T NF alpha and TGF beta antagonistically modulate the expression of adhe sion molecules. VCAM-1 and ICAM-1 contribute to adhesion of T lymphocy tes to chondrocytes, and may thus participate in host defense mechanis ms during inflammatory joint conditions such as rheumatoid arthritis a nd after cartilage transplantation.