Adhesion molecule expression in human synovial tissue

Abstract

Objective. We have previously shown that E‐selectin is expressed on endothelium in rheumatoid arthritis (RA) synovial tissues, and hence may be important in recruitment of leukocytes into the inflamed joint. In the present study, we determined whether other cellular adhesion molecules, including selectins and members of the integrin and immunoglobulin supergene families, are expressed in frozen synovium. Methods. We employed immunohistochemical staining to determine the distribution of CD31 (PECAM), CD44 (hyaluronate receptor), CD62 (P‐selectin), Leu‐8 (L‐selectin), and the integrin subunits α5 (VLA‐5), α6 (VLA‐6), β1 (VLA 1–6), and β3 (vitronectin receptor), in synovial tissue from 9 RA and 9 osteoarthritis (OA) patients, and from 3 normal (NL) subjects. Results. P‐selectin was expressed on vascular endothelium in all synovial tissues examined. L‐selectin and α5‐integrin, while expressed on a variety of cell types, were not differentially expressed on RA synovial tissues. Integrin subunits α6 and β1 were down‐regulated on some RA synovial tissue components. In contrast, CD31 was expressed to a greater extent on RA than on OA lining cells and macrophages (P < 0.05). CD44 was expressed to a greater extent on RA or OA macrophages, lining cells, and fibroblasts compared with NL (P < 0.05). Integrin subunit β3 was strongly expressed on RA synovial blood vessels compared with NL (P < 0.05). Conclusion. The expression of integrins VLA 1–6, and selectins P and L is not up‐regulated in RA synovial tissues. CD31 and CD44 are up‐regulated on RA macrophages and lining cells, CD44 on RA fibroblasts, and β3‐integrin on RA blood vessels. The up‐regulation of CD31, CD44, and β3‐integrin in RA synovial tissues may help tip the balance of adhesive interactions toward passage and retention of leukocytes in the inflamed joint.

Invasive fibroblast‐like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors?

“…The fibroblast-like synoviocytes (FLS) (3)(4)(5). These proteins are also expressed by fibroblasts in the sublining region.…”

“…Intercellular adhesion molecule 1 (ICAM-l), the hyaluronic acid receptor (CD44), PIintegrins (including the fibronectin and vascular cell adhesion molecule 1 [VCAM-I] receptors), and P3-integrins (such as the vitronectin receptor) are expressed by the RA intimal lining in amounts that are higher than those in normal tissue (3)(4)(5). These proteins are also expressed by fibroblasts in the sublining region.…”

“…Type B Gary S . Firestein, MD, Division of Rheurnatology, University of California at San Diego School of Medicine.Address reprint requests to Gary S. Firestein, MD, Division of Rheumatology, University of California at San Diego School of Medicine, #0656, 9500 Gilman Drive, La Jolla, CA 92093.Submitted for publication February 20, 1996; accepted in revised form May 15, 1996. cells have the morphologic appearance of fibroblasts as well as the structural machinery to synthesize and secrete an impressive array of products, including proteoglycans, cytokines, arachidonic acid metabolites, and metalloproteinases.The fibroblast-like synoviocytes (FLS) (3)(4)(5). These proteins are also expressed by fibroblasts in the sublining region.…”

Selectins and integrins but not platelet–endothelial cell adhesion molecule‐1 regulate opioid inhibition of inflammatory pain

“…Thereafter, the cells migrate through the endothelium engaging immunoglobulin superfamily members, predominately platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) on leukocytes and endothelium (Butcher & Picker, 1996;von Andrian & Mackay, 2000). All these molecules are constitutively expressed and are upregulated in inflammation, except L-selectin, which is rapidly shed upon activation (Johnson et al, 1993;Schaible et al, 1994;Bennett et al, 1996;Issekutz TB et al, 1996;Mousa et al, 2000). Their blockade has been proposed as a novel anti-inflammatory strategy (Bogen et al, 1994;Issekutz AC et al, 1996;.…”

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

“…In addition, immunohistochemical studies have demonstrated increased expression of VCAM-1 and ICAM-1 on RA synovial endothelial cells, although in contrast to E-selectin, staining was also detectable on other cell types, including synovial tissue macrophages, dendritic cells, fibroblasts, and some lymphocytes (4)(5)(6). Expression of these adhesion molecules is dramatically upregulated on a number of cell types, including endothelium, by proinflammatory cytokines such as tumor necrosis factor a (TNFa) and interleukin-1 (IL-1) (3), which we and others have demonstrated to play a central role in RA.…”