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Objective. To define the synovial distribution of the novel leukointegrin αd/CD18, and compare this with other members of the β2‐integrin family of adhesion molecules, and their counter‐receptors. Methods. Monoclonal antibodies to the CD3, CD14, CD29, CD68, β2‐integrin, and immunoglobulin supergene families were used to immunohistologically define the distribution of these molecules in synovial tissue samples from normal subjects and osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Results. The normal synovial lining cell layer (SLC) expresses CD68, vascular cell adhesion molecule 1, β1‐integrin (CD29), the β2‐integrins CD11b/CD18 (αm/β2, Mac‐1), and α/CD18, whereas CD11a/CD18 (αL/β2, lymphocyte function‐associated antigen 1) and CD11c/CD18 (αx/β2, gp150/95) expression is generally absent. In RA synovitis, expression of β2‐integrins in the SLC increases in proportion to the degree of hyperplasia. The ratio of cells in the SLC which express CD11c/CD18 increases substantially, approaching that of CD11b/CD18 and αd/CD18, while there is minimal increase in CD11a/CD18 expression. In the sublining areas of the tissues, aggregates and diffuse infiltrates of CD3/CD11a/ICAM‐3+ lymphocytes are interspersed among CD68/CD14/CD11b/αd+ macrophages. A number of aggregates demonstrate intense αd staining of the lymphocytes. The synovial endothelium variably expresses intercellular adhesion molecule‐1 (ICAM‐1), ICAM‐2, and vascular cell adhesion molecule 1 (VCAM‐1), with minimal evidence of ICAM‐3 expression. Conclusion. The leukointegrin αd/CD18 is expressed constitutively by synovial macrophages and macrophage‐like lining cells. In rheumatoid synovitis, the intense coexpression of this integrin and its known counter‐receptor, ICAM‐3, in the inflammatory infiltrates, suggests a potential role for this adhesion pathway in cellular interactions occurring the synovium.

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Objective. To study the distribution of intercellular adhesion molecule receptor (ICAM-R, or ICAM3), a novel ligand for the leukointegrin lymphocyte function-associated antigen 1 (LFA-l), in normal and rheumatoid synovial membranes and to compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion molecule 1 (VCAM-l), 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 conHani El-Gabalawy, MD: The University of Manitoba, Winnipeg, Manitoba, Canada; Michael Gallatin, PhD: ICOS Corporation, Seattle, Washington; Rosemay Vazeux, PhD: ICOS Corporation; Gary Peterman, PhD: ICOS Corporation; John Wilkins, P h D University of Manitoba.Address reprint requests to Hani El-Gabalawy, MD, Rheumatic Disease Unit, 800 Sherbrook Street, Winnipeg, Manitoba R3A 1M4, Canada.Submitted for publication March 31, 1993; accepted in revised form November 30, 1993. trast, 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.Chronic inflammatory lesions such as rheumatoid synovitis require ongoing recruitment and retention of leukocytes from the vascular space. A critical initial step involves the adhesion of leukocytes to vascular endothelium (1-3). This is currently thought to be regulated by a cascade of molecular interactions occurring between leukocyte membrane receptors and endothelial counter-receptors, many of which are inducible in their expression. Several endothelial adhesion molecules have been well characterized and shown to participate in leukocyte attachment. These include the endothelial leukocyte adhesion molecule 1 (ELAM-1, or E-selectin) (4), intercellular adhesion molec...