ENDOTHELIAL-CELLS ARE THE MAJOR SOURCE OF SICAN-1 IN RHEUMATOID SYNOVIAL TISSUE

The objective of this research was to investigate the cellular source of soluble ICAM-1 (siCAM-1) from rheumatoid synovial tissue (RS) and i ts relation to sICAM-1 in synovial fluid (SF) and serum, and to study the expression of ICAM-1 in isolated cells of RS. sICAM-1 was determin ed by using the enzyme-linked immunosorbent assay (ELISA) and Western blot analysis in supernatants from RS cultured for short periods (n = 19), in SF (n = 7) and in serum (n = 19). ICAM-1 expression, vasculari zation and inflammatory infiltration (CD3, CD68, CD22) were characteri zed immunohistochemically in cytospin preparations (n = 18), cryosecti ons (n = 18) and in conventionally stained paraffin sections (n = 19) of RS. The degree of RS vascularization was analysed morphometrically in immunohistochemically stained cryosections (factor VIII related ant igen). We found 90-kD sICAM-1 in supernatants of cultured cells, in SF and in sera. sICAM-1 in cellular supernatant correlated significantly (P < 0.01) with SF sICAM-1. The amount of sICAM in cellular supernata nts showed no correlation to the score of inflammatory infiltration, b ut correlated significantly (P < 0.001) with the vascularization index of RS. The percentage of ICAM-1-expressing cells correlated significa ntly (P < 0.001) with the percentage of CD68-positive macrophages, but not with CD3- and CD22-positive lymphocytes. Macrophages, multinuclea ted giant cells and endothelial cells exhibited a higher expression of ICAM-1 as compared to lymphocytes and fibroblasts. The differential e xpression of ICAM-1 on infiltrating leucocytes and resident cells of R S indicates a functional role of ICAM-1 in the local inflammatory proc ess. SF sICAM-1 originated in RSI but serum sICAM-1 did not. Shedding of sICAM-1 by RS was independent of inflammatory infiltration, but dep ended on the degree of vascularization, indicating that endothelial ce lls are the major source of sICAM-1 in RS.