Endothelial cells are the major source of sICAM-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 its 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 determined 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, vascularization and inflammatory infiltration (CD3, CD68, CD22) were characterized immunohistochemically in cytospin preparations (n = 18), cryosections (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 antigen). 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 supernatants showed no correlation to the score of inflammatory infiltration, but correlated significantly (P < 0.001) with the vascularization index of RS. The percentage of ICAM-1-expressing cells correlated significantly (P < 0.001) with the percentage of CD68-positive macrophages, but not with CD3- and CD22-positive lymphocytes. Macrophages, multinucleated giant cells and endothelial cells exhibited a higher expression of ICAM-1 as compared to lymphocytes and fibroblasts. The differential expression of ICAM-1 on infiltrating leucocytes and resident cells of RS indicates a functional role of ICAM-1 in the local inflammatory process. SF sICAM-1 originated in RS, but serum sICAM-1 did not. Shedding of sICAM-1 by RS was independent of inflammatory infiltration, but depended on the degree of vascularization, indicating that endothelial cells are the major source of sICAM-1 in RS.