SYNOVIAL DISTRIBUTION OF ALPHA(D) CD18, A NOVEL LEUKOINTEGRIN - COMPARISON WITH OTHER INTEGRINS AND THEIR LIGANDS/

Objective. To define the synovial distribution of the novel leukointeg rin alpha(d)/CD18, and compare this with other members of the beta(2)- integrin family of adhesion molecules, and their counter-receptors. Me thods. Monoclonal antibodies to the CD3, CD14, CD29, CD68; beta(2)-int egrin, and immunoglobulin Supergene families were used to immunohistol ogically define the distribution of these molecules in synovial tissue samples from normal subjects and osteoarthritis (OA) and rheumatoid a rthritis (RA) patients. Results. The normal synovial lining cell layer (SLC) expresses CD68, vascular cell adhesion molecule 1, beta(1)-inte grid (CD29), the beta(2)-integrins CD11b/CD18 (alpha(m)/beta(2), Mac-1 ), and alpha(d)/CD18, whereas CD11a/CD18 (alpha(1)/beta(2), lymphocyte function-associated antigen 1) and CD11c/CD18 (alpha(x)/beta(2), gp15 0/95) expression is generally absent. In RA synovitis, expression of b eta(2)-integrins in the SLC increases in proportion to the degree of h yperplasia, The ratio of cells in the SLC which express CD11c/CD18 inc reases substantially, approaching that of CD11b/CD18 and alpha(d)/CD18 , while there is minimal increase in CD11a/CD18 expression. In the sub lining areas of the tissues, aggregates and diffuse infiltrates of CD3 /CD11a/ICAM-3+ lymphocytes are interspersed among CD68/CD14/CD11b/alph a(d)+ macrophages. A number of aggregates demonstrate intense alpha(d) staining of the lymphocytes. The synovial endothelium variably expres ses intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular c ell adhesion molecule 1 (VCAM-1), with minimal evidence of ICAM-3 expr ession. Conclusion. The leukointegrin alpha(d)/CD18 is expressed const itutively by synovial macrophages add macrophage-like lining cells, In rheumatoid synovitis, the intense coexpression of this integrin and i ts known counter-receptor, ICAM-3, in the inflammatory infiltrates, su ggests a potential role for this adhesion pathway in cellular interact ions occurring the synovium.