Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid and nonrheumatoid synovium. Comparison with other adhesion molecules

Abstract

Objective: To study the distribution of intercellular adhesion molecule receptor (ICAM-R, or ICAM-3), a novel ligand for the leukointegrin lymphocyte function-associated antigen 1 (LFA-1), in normal and rheumatoid synovial membranes and to compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1).

Methods: We performed immunohistochemical analyses of frozen sections of normal and rheumatoid synovial tissue using monoclonal antibodies to the molecules examined.

Results: ICAM-1 staining was detectable on the vascular endothelium and the synovial lining cells of both normal and rheumatoid synovial membranes. A variable proportion of lymphocytes infiltrating rheumatoid tissues expressed ICAM-1, ICAM-2 staining was demonstrable in the vascular endothelium of both normal and inflamed tissues, the latter demonstrating a significantly higher proportion of positive vessels. ELAM-1 staining was not detectable in normal synovial membranes but was seen on the endothelium of a limited number of rheumatoid synovial vessels, usually close to the synovial lining cell layer. VCAM-1 staining was intense in both normal and rheumatoid synovial lining cells, but vascular staining was weak in both. In contrast, ICAM-R staining was not detected in association with any synovial blood vessels, but was widely expressed by lymphocytes and macrophages. Cells of the lining layer did not stain for ICAM-R.

Conclusion: Although ICAM-R is a ligand for LFA-1 and shares considerable sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by the endothelium of normal or inflamed synovial vessels. Intense expression of ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may play a role in processes requiring cell-cell contact, such as antigen presentation and homotypic aggregation.