Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA.
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PMID:Human bone marrow stromal cell lines from myeloma and rheumatoid arthritis that can support murine pre-B cell growth. 128 Dec 1

Cell and matrix adhesion of lymphocytes participates in homing, migration and accumulation of these cells in inflamed tissues as well as in the generation of immune and inflammatory responses. In inflamed joints of rheumatoid arthritis (RA) patients, lymphocytes accumulate in the synovial membrane and the synovial fluid. In the present study we have analyzed the expression of integrins and other adhesion molecules in synovial fluid lymphocytes (RA-SFL) and paired peripheral blood lymphocytes (RA-PBL) from 21 RA patients by immunofluorescence flow cytometry. We have also investigated the expression of these adhesion molecules on peripheral blood lymphocytes obtained from 13 sex- and age-matched healthy controls (CO-PBL). RA-SFL, which consisted mostly of T cells, showed higher expression of the integrin subunits beta 1 (CD29), VLA-1 alpha, -3 alpha, -4 alpha, -5 alpha and -6 alpha when compared to RA-PBL. In turn, RA-PBL showed lower expression of these molecules than CO-PBL. The expression of the immunoglobulin-related molecules CD2, CD54 (ICAM-1) and CD58 (LFA-3) was higher on RA-SFL when compared to RA-PBL or CO-PBL, and similar results were obtained with the beta 2 integrin subunits CD11a and CD18. In contrast, L-selectin (LECAM-1) and ICAM-2 were expressed at much lower levels on RA-SFL than on RA-PBL or CO-PBL. CD44, a receptor for hyaluronic acid and collagen, was expressed by most RA-SFL, RA-PBL and CO-PBL cells but at higher density on RA-SFL. The results indicate that RA-SFL express a distinct array of adhesion molecules, similar to the one of memory T lymphocytes. This characteristic phenotype may contribute to the lymphocytic infiltration of the synovium and to the pathogenesis of RA.
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PMID:Integrins and other adhesion molecules on lymphocytes from synovial fluid and peripheral blood of rheumatoid arthritis patients. 138 54

The hyaluronate receptor (CD44) molecule is a multifunctional cell surface protein involved in T cell activation, monocyte cytokine release, fibroblast locomotion, and lymphocyte binding to high endothelial venules. To study the roles CD44 molecules play in inflammatory synovitis, we measured expression of CD44 in inflamed and noninflamed synovial fluid and tissue, using indirect immunofluorescence assays on tissue sections and quantitative Western blot analysis. The ability of purified CD44 protein to modulate T cell responses was tested in T cell activation assays in which CD44-containing liposomes were added in vitro. CD44 was widely expressed on many synovial cell types, and synovial tissue from rheumatoid arthritis (RA) patients contained 3.5 times more CD44 than tissue from osteoarthritis patients and 10.7 times more than tissue from patients with joint trauma. The level of soluble CD44 in RA synovial fluid was elevated only in fluids with low cell counts (less than or equal to 7,000/mm3), and not in RA synovial fluid with higher cell counts. Soluble purified CD44 protein in liposomes partially suppressed T cell activation in vitro. These data demonstrate that CD44 is up-regulated on many synovial cell types in patients with RA, and that the level of CD44 present in synovial tissue is related to the degree of synovial inflammation. Determination of ways to inhibit the proinflammatory functions of immune cell membrane CD44 molecules may provide new therapeutic modalities for RA.
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PMID:Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis. 171 88

The role of several adhesion molecules for lymphocyte-endothelial interactions in the synovia of rheumatoid arthritis patients was studied using the frozen section assay. Partial inhibition of lymphocyte binding to endothelium of synovial sections could be observed with antibodies against CD44, L-selectin, and beta 1- and beta 2-integrins, pointing to the participation of several adhesion molecules in the regulation of lymphocyte immigration into inflamed synovia rather than the presence of a unique homing receptor. Different degrees of inhibition were found within a series of antibodies against alpha 4- and beta 1-integrins known to have functional effects in other interaction systems. In addition, increased binding to endothelial cells was induced when lymphocytes were pretreated with TS2/16 anti-beta 1 IgG, whereas binding to non-endothelial components of synovia was increased after treatment with HP 2/4 (anti-alpha 4) Fab. The data suggest a multifunctional role of alpha 4/beta 1-integrins in directly mediating adhesion as well as regulating adhesive interactions in the rheumatoid synovia.
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PMID:Lymphocyte-endothelial interactions in inflamed synovia: involvement of several adhesion molecules and integrin epitopes. 768 80

The immunophenotype of lining and subintimal synovial mononuclear phagocytes (MP) of rheumatoid arthritis (RA) were sought by immunohistology and compared with osteoarthritis (OA) tissue in order to determine the significance of MPs in the pathobiology of RA. Almost all the lining cells (SLCs) in RA consisted of MPs (80 to 90% expressing CD45/CD14/CD68). A major proportion of the interaggregate areas of the rheumatoid subintima was also made of MP cells (50 to 70% expressing CD14/CD68). A marked variation in the immunohistological reaction of antibodies reacting within intimal MPs and between intimal and subintimal MPs was found. Intimal MPs expressed a wide range of macrophage-associated antigens, including receptors for Fc (CD16, CD32, CD64) and complement (CD35, CD11b, CD11c) as well as several integrin and non-integrin cell adhesion molecules (CD29/CD49b, CD49d, CD49f, CD51/CD61, CD11a, CD31, CD54, CD44, CD9, CD63). The monocyte marker, CD14, was down-regulated on SLCs in both RA and OA. When compared to intimal expression of leucocyte common antigen (CD45), CD68, a pan-macrophage maturation antigen, was found to be an unreliable macrophage antigen in OA intima. There was no difference in antigenic phenotype of SLCs in inflammatory and non-inflammatory OA with early activation markers (CD25, CD71) mainly present on MPs. In RA, synovial MPs showed increased expression of activation, maturation and functional antigens suggesting that they are rapidly and fully activated. The fact that their recruitment was independent of the degree of lymphocyte infiltration further emphasises the central importance of synovial MPs in RA.
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PMID:[Macrophages in rheumatoid synovial membrane: an update]. 801 31

The role of adhesion molecules for lymphocyte-endothelial interactions in the synovia of rheumatoid arthritis patients was studied using the frozen section assay. Partial inhibition of lymphocyte binding to endothelium of synovial sections could be observed with antibodies against CD44, L-selectin, beta 1 and beta 2 integrins, pointing to the participation of several adhesion molecules in the regulation of lymphocyte immigration into inflamed synovia.
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PMID:[Adhesion molecules and homing in inflamed synovia]. 834 73

Hyaluronan is a constituent of the extracellular matrix of connective tissue and is actively synthesized during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of hyaluronan are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, hyaluronan has been implicated as an important substrate for migration of adhesion of leukocytes during inflammation. A human hyaluronan synthase (HuHAS1) cDNA was isolated by a functional expression cloning approach. Transfection of CHO cells conferred hyaluronidase-sensitive adhesiveness of a mucosal T cell line via the lymphocyte hyaluronan receptor, CD44, as well as increased hyaluronan levels in the cultures of transfected cells. The HuHAS1 amino acid sequence shows considerable homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase from Xenopus laevis (DG42), and is the human homolog of a recently described murine hyaluronan synthase.
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PMID:Functional cloning of the cDNA for a human hyaluronan synthase. 879 44

Adhesion molecules play important roles in immune reactions and inflammatory processes and may constitute attractive targets for immunomodulatory approaches. In this study, blocking mAbs against a series of adhesion molecules were tested for their therapeutic effect on developing arthritis in a mouse model. MAbs were given for a period of 4 weeks at the time of exspected incidence of visible disease symptoms, i.e. 4 weeks after priming with collagen type II. A significant reduction of incidence down to values of 13% and 29% of the controls was obtained with mAbs against CD44 and alpha 4-integrin, respectively, during an observation time of 13 weeks. MAbs against CD4 and LFA-1 resulted only in weaker, non-significant effects or a delay in the incidence. MAbs against other molecules including L-selectin, ICAM-1 or VCAM-1 were not effective. The development of antibodies against collagen type II, collagen type I, proteoglycans and the immunogen, bovine collagen type II was affected by mAb treatment to a different extent. In this case, the anti CD4 mAb was the most effective, followed by the anti alpha 4-antibodies in most cases, whereas anti CD44 showed less clear effects on the development of humoral responses. In a skin delayed type hypersensitivity model analyzed for comparison, mAbs against LFA-1/ICAM-1 and alpha 4-integrin showed the largest effects on ear swelling. These data show that mAbs against several adhesion molecules are able to block selectively distinct aspects of immune reactions, and that CD44 and alpha 4-integrins could be promising targets for an immunotherapy of rheumatoid arthritis with receptor-interfering agents.
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PMID:Therapeutic effects of antibodies against adhesion molecules in murine collagen type II-induced arthritis. 885 15

Rheumatoid pseudocysts of which pathogenesis are not well known, are commonly observed in the major joints of the body, especially knees in rheumatoid patients. This report investigated the pseudocysts in the knee of a rheumatoid patient radiologically and immunohistochemically. A sixty-three-year-old woman with rheumatoid arthritis who had pseudocysts in the femoral lateral condyle and tibial plateau was hospitalized to have the lesions surgically removed. The MRI findings showed a connection between the pseudocysts and the joint cavity. A window of 1 x 1 cm2 was made at the tibial anterior cortex and the contents of the pseudocyst were resected and hydroxyapatite granules were inserted into the lesion after the removal of the pseudocyst tissue. In the histological findings, the specimen from the tibial pseudocyst revealed fibrous connective tissue with a few inflammatory cells, while the synovial specimen revealed the fibrous tissue with intense inflammatory cells infiltration forming lymphoid follicules. In immunohistochemical findings, both specimens showed positive with anti-HLA class I, anti-HLA DR, anti-CD44 and anti-HSP70 antibodies. The pathological findings of the pseudocystic lesion were similar to those of synovia, and it was considered that the synovia had invaded into the bone and formed the pseudocystic lesion. The MRI findings also support this hypothesis. The pseudocystic lesion was surrounded by bone and it was isolated from cytokain-rich joint effusion. This isolation from rheumatic joint effusion may explain the weaker inflammation of the pseudocystic lesion than that of synovia.
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PMID:[A case study of immunohistochemical findings of rheumatic pseudocystic lesions in the femoral lateral condyle and tibial plateau--the comparison with synovial lesions]. 891 Oct 84

An Epstein-Barr virus (EBV)-infected fibroblast line, designated DSEK, was spontaneously established from synovial tissue of a patient with rheumatoid arthritis (RA). DSEK cells expressed EBV nuclear antigens EBNA-1 and EBNA-2 and latent membrane protein LMP-1. Cell surface markers of DSEK cells were similar to those of EBV-negative fibroblast clones derived from synoviocytes and were negative for lymphocyte and macrophage markers. DSEK cells expressed CD44, CD58, and HLA-DR antigens and spontaneously produced interleukin-10 basic fibroblast growth factor and transforming growth factor beta1. These results indicate that rheumatoid synoviocytes can be a target for EBV infection and suggest that EBV may play a role in the pathogenesis of RA.
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PMID:Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient. 903 86


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