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 leukointegrin alpha d/CD18, and compare this with other members of the beta 2-integrin family of adhesion molecules, and their counter-receptors.


METHODS
Monoclonal antibodies to the CD3, CD14, CD29, CD68, beta 2-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, beta 1-integrin (CD29), the beta 2-integrins CD11b/CD18 (alpha m/beta 2, Mac-1), and alpha d/CD18, whereas CD11a/CD18 (alpha L/beta 2, lymphocyte function-associated antigen 1) and CD11c/CD18 (alpha x/beta 2, gp150/95) expression is generally absent. In RA synovitis, expression of beta 2-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 alpha d/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/alpha d+ macrophages. A number of aggregates demonstrate intense alpha d 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.


CONCLUSIONS
The leukointegrin alpha d/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.
University of Manitoba, Section of Rheumatology, Winnipeg, Canada.
H
H
el-Gabalawy
J
J
Canvin
G M
GM
Ma
M
M
Van der Vieren
P
P
Hoffman
M
M
Gallatin
J
J
Wilkins
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001168:Arthritis / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001808:Blood Vessels / Q000737:chemistry / Q000276:immunology; D018821:CD18 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000098:blood supply / Q000737:chemistry*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human