Differential distribution of intercellular adhesion molecules (ICAM-1, ICAM-2, and ICAM-3) and the MS-1 antigen in normal and diseased human synovia. Their possible pathogenetic and clinical significance in rheumatoid arthritis.
OBJECTIVE
Cellular adhesion and differentiation molecules (CAMs) may play a role in the recruitment and retention of inflammatory cells into rheumatoid arthritis synovial tissue (RA ST). In order to determine if certain CAMs are up-regulated in RA ST compared with normal ST, we studied the distribution of intercellular adhesion molecules (ICAMs) 1, 2, and 3 in ST. We also studied the MS-1 antigen since it is preferentially expressed on discontinuous endothelia, such as those found in RA ST; MS-1 is also expressed differentially upon cytokine activation of cells in vitro or in pathologic conditions in situ. Thus, we postulated a possible similarity between MS-1 and ICAM-1 expression in inflamed ST.


METHODS
Immunohistochemical analysis was used to determine the distribution of ICAMs and MS-1 in ST from 10 patients with RA, 10 with osteoarthritis (OA), and 4 normal individuals.


RESULTS
ICAM-1 expression was found on significantly more RA ST endothelial cells compared with normal cells, as well as on RA ST macrophages and lining cells. ICAM-2, also found on endothelial cells, showed no differential staining pattern. ICAM-3 was present on RA ST macrophages and lining cells as well as on some RA and OA endothelial cells. The MS-1 antigen was present on most RA and OA ST endothelia, lining cells, and macrophages. ICAM-1 expression and MS-1 expression in the lining layer were positively correlated in both RA and OA.


CONCLUSIONS
ICAM-1, while found mainly on endothelial cells, is up-regulated on RA ST macrophages and lining cells, suggesting a role for these cells in the infiltration and tissue damage seen in the RA ST: ICAM-3, which is present mainly on normal resting leukocytes but not on normal endothelium, is expressed by some diseased ST leukocytes and endothelial cells. MS-1 is also found on the RA ST specialized, fenestrated endothelium, on macrophages, and in the lining layer. These results suggest that the differential expression of ICAMs and MS-1 in RA ST compared with normal ST might play a special role in the pathogenesis of RA.
Szekanecz
Z
Z
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Haines
G K
GK
Lin
T R
TR
Harlow
L A
LA
Goerdt
S
S
Rayan
G
G
Koch
A E
AE
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism*; D012016:Reference Values; D013583:Synovial Membrane / Q000378:metabolism*; D014018:Tissue Distribution
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins