Objective. A new animal model was used to study the interaction between rheumatoid synovial cells and cartilage and to explore the cellular basis of rheumatoid joint destruction.Methods. Fresh synovial tissue derived from patients with rheumatoid arthritis was implanted with normal human cartilage into SCID mice, either subcutaneously or under the renal capsule, for up to 304 days. The implants were analyzed by light and electron microscopy, as well as by immunohistochemistry and in situ hybridization.Results. Human synovial tissue and cartilage implanted in SCID mice are maintained by the animals for up to 304 days. After 35 days, focal erosions occur at the site of attachment of synovial lining cells to the cartilage. After 105 days, a pannus-like formation, consisting of proliferating synovial fibrpblast-like cells invading the cartilage, is observed. The fibroblast nature of these cells was supported by observation of only focal expression of the macrophage markers CD14 and CD68. Cells at the immediate site of cartilage destruction express messenger RNA for cathepsin L, whereas cathepsin D messenger RNA was detected in subsynovial regions away from the site of destruction. The human origin of the tissue involved in cartilage destruction was
Objective. To compare the expression of cathepsin L, cathepsin D, and collagenase messenger RNA (mRNA) in synovial specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).Methods. The expression of cathepsins L and D as well as collagenase mRNA in synovial tissues from 8 patients with RA, 6 patients with OA, and 2 patients with noninflamed joints was evaluated using in situ hybridization with digoxigenin-labeled RNA probes.Results. Both RA and OA synovial tissue expressed cathepsins L and D as well as collagenase mRNA. The expression of the cathepsins was markedly higher in interstitial regions and, to some extent, in perivascular infiltrates of RA synovial tissue compared with OA specimens. Conclusion. Cathepsins L and D mRNA are expressed differently in RA and OA synovial tissues, supporting the concept that these enzymes may contribute to the influx of mononuclear cells into RA synovium. Moreover, the data reveal that the expression of collagenase and cathepsins in RA and OA synovial lining is otherwise largely similar, and suggest that the adhesion
Systemic lupus erythematosus is an autoimmune disease of unknown etiology. Research efforts of the last few years have mainly focused on basic molecular and cellular pathogenetic processes of the disease. Consequently, this paper reviews the etiopathogenetic hallmarks, such as impaired amount and presentation of nuclear antigens, production of antinuclear antibodies by T-cell-dependent B cell stimulation and organ damage by anti-dsDNA antibodies or immune complexes that are discussed at the present time. In summary, the hypothesis of a dysregulation of apoptotic cell clearance is strongly supported and broadly discussed.
Objective. To examine the de novo synthesis and cellular distribution of the E-selectin adhesion molecule in synovial tissues obtained from patients with rheumatoid arthritis (RA).Methods. Immunohistochemistry techniques combined with in situ hybridization were used to examine RA synovium.Results. There were numerous endothelial cells positive for E-selectin and E-selectin messenger RNA in the RA synovial membranes. Moreover, E-selectin expression appeared to correlate with inflammatory activity.
Conclusion. The strong vascular expression of E-selectin indicates an activation of endothelial cells in the recruitment of cells associated with the chronic inflammation of RA.The synovial membrane of patients with rheumatoid arthritis (RA) shows marked hyperplasia of the synovial lining cells and an accumulation of CD4+ T cells in the subsynovial tissue (I). A role for a number of vascular adhesion molecules, including intercellular adhesion molecule I and its receptor CDl 1a,b/CD18, vascular cell adhesion molecule 1 (VCAM-1) and its receptor very late activation antigen 4 (CD49d/CD29), and endothelial leukocyte adhesion molecule 1 (ELAM-1 ; which adheres to sialylated Lewis X sugars
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