title: Endothelial cells are the major source of sICAM-1 in rheumatoid synovial tissue.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Würzburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Krenn
authors.forename: J
authors.initials: J
authors.lastname: Schedel
authors.forename: A
authors.initials: A
authors.lastname: Döring
authors.forename: H I
authors.initials: HI
authors.lastname: Huppertz
authors.forename: F
authors.initials: F
authors.lastname: Gohlke
authors.forename: H P
authors.initials: HP
authors.lastname: Tony
authors.forename: H P
authors.initials: HP
authors.lastname: Vollmers
authors.forename: H K
authors.initials: HK
authors.lastname: Müller-Hermelink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*
chemical_list: D018799:Intercellular Adhesion Molecule-1