DigitalUM :: Browsing by Subject "Rheumatoid arthritis"

Browsing by Subject "Rheumatoid arthritis"

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Open Access
Abnormal distribution of CD45 isoforms expressed by CD4+ and CD8+ T cells in rheumatoid arthritis
(Murcia : F. Hernández, 2000) Mamoune, A.; Durand, V.; Le Goff, P.; Pennec, Y.L.; Youinou, P.; Le Corre, R.
CD45RO+ T cells are referred to as memory or helper-inducer while CD45RA+ T cells are regarded as naive or suppressor-inducer T cells. The former population predominates in the peripheral blood and even more in the synovial fluid of patients with rheumatoid arthritis, to the expense of the latter population. Within the CD45RB+ compartment, there appears to be more of the fully-differentiated than of the early-differentiated CD4+ T cells. In spite of the fact that these lymphocytes are close to undergoing apoptosis, this programmed cell death is inhibited in the rheumatoid synovium.
Open Access
Angiogenesis in rheumatoid arthritis
(Murcia : F. Hernández, 2006) Maruotti, Nicola; Cantatore, F.P.; Crivellato, E.; Vacca, A.; Ribatti, Doménico
There is much evidence that rheumatoid arthritis is closely linked to angiogenesis. Important angiogenic mediators have been demonstrated in synovium and tenosynovium of rheumatoid joints. VEGF (Vascular Endothelial Growth Factor), expressed in response to soluble mediators such as cytokines and growth factors and its receptors are the best characterized system in the angiogenesis regulation of rheumatoid joints. Moreover, other angiogenic mediators such as platelet-derived growth factor (PDGF), fibroblast growth factor-2 (FGF-2), epidermal growth factor (EGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), transforming growth factor beta (TGF-ß), tumor necrosis factor alpha (TNF- a), interleukin-1 (IL-1), IL-6, IL-8, IL-13, IL-15, IL-18, angiogenin, platelet activating factor (PAF), angiopoietin, soluble adhesion molecules, endothelial mediator (endoglin) play an important role in angiogenesis in rheumatoid arthritis. On the other hand, endostatin, thrombospondin-1 and -2 are angiogenic inhibitors in rheumatoid arthritis. The persistence of inflammation in rheumatoid joints is a consequence of an imbalance between these inducers and inhibitors of angiogenesis.
Open Access
Crosstalk between synovial macrophages and fibroblasts in rheumatoid arthritis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Saeki, Noritaka; Ima, Yuuki
Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of joints. Abnormally activated cells such as synovial macrophages and synovial fibroblasts induce RA pathogenesis and ultimately joint destruction. Since macrophages can change their own characteristics depending on the microenvironmental condition, it has been suggested that activation and remission of RA are regulated by crosstalk between synovial macrophages and other cells. Moreover, recent findings of heterogeneity of synovial macrophages and fibroblasts support the idea that complex interactions regulate RA from its onset to remission. Importantly, an understanding of the intercellular crosstalk in RA is far from complete. Here, we summarize the molecular mechanisms underlying the pathological development of RA with particular reference to the crosstalk between synovial macrophages and fibroblasts.
Open Access
Detection of sarcolectin-specific receptors like the cytokine macrophage migration inhibitory factor in rheumatoid nodules migration inhibitory factor in rheumatoid nodules
(Murcia : F. Hernández, 1999) Zschabitz, A.; Gabius, H.J.; Zeng, F.Y.; Kunt, T.; Martens, K.D.; Koepp, H.; Fassbender, H.G.; Stofft, E.
The objective of this study was the evaluation of the relation between the N-acetylneuraminic acid-binding endogenous lectin sarcolectin and the cytokine macrophage migration inhibitory factor (MIF) during development of rheumatoid nodules (RN) in seropositive rheumatoid arthritis (RA). Sarcolectin was purified and biotinylated. The binding patterns of this probe were analyzed in RN from patients with RA (n=23) and compared with the distribution of antibodies with specificity for MIF, fibrin, fibronectin. In early RN, all areas of the inflammatory tissue displayed presence of receptors for sarcolectin. Macrophages were especially positive. In mature rheumatoid nodules binding of sarcolectin was restricted to the periphery of necrotic areas, to endothelial cells and perivascular connective tissue of marginal zones. Distribution patterns of MIF were similiar but not identical. The histological staining characteristics demonstrate sarcolectin-binding receptors in RN that are altered upon disease progression. The finding suggests that specific interactions between this endogenous lectin and MIF may be involved in the course of RA.
Open Access
Histopathology and molecular pathology of synovial B-lymphocytes in rheumatoid arthritis
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Krenn, V.; Souto-Carneiro, M. M.; Kim, H.- J.; Berek, C.; Starostik, P.; König, A.; Harms, H.; Müller-Hermelink, H. K.
B-cells of the rheumatoid synovial tissue are a constant part of and, in some histopathological subtypes, the dominant population of the inflammatory infiltrate, located in the region of tissue destruction. The pattern of B-cell distribution and the relationship to the corresponding antigen-presenting cells (follicular dendritic reticulum cells: FOCs) show a great variety. Bcells may exhibit (i) a follicular organization forming secondary follicles; (ii) follicle-like patterns with irregularly formed FOC networks, and (iii) a diffuse pattern of isolated FOCs. Molecular analysis of immunoglobulin YH and YL genes from human synovial B-cell hybridomas and synovial tissue demonstrates somatic mutations due to antigen activation. The FOC formations in the synovial tissue may therefore serve as an environment for B-cell maturation, which is involved in the generation of autoantibodies. An autoantibody is defined as "pathogenic" if it fulfills the Witebsky-Rose-Koch criteria for classical autoimmune diseases: definition of the autoantibody; induction of the disease by transfer of the autoantibody; and isolation of the autoantibody from the disease-specific lesion. B-cells from rheumatoid synovial tissue show specificity for FcIgG, type II collagen, COMP, sONA, tetanus toxoid , mitochondrial antigens (M2), filaggrin and bacterial HSPs. The contributions of these antigens to the pathogenesis of RA are still hypothetical. A possible contribution could derive from crossreactivity and epitope mimicry: due to crossreaction, an antibody directed originally against a foreign infectious agent could react with epitopes from articular tissues, perpetuating the local inflammatory process. The characteristic distribution pattern, the localisation within the area of tissue destruction, the hypermutated IgYH and IgYL genes, and their exclusive function to recognize conformation-dependent antigens suggest a central role for B-cells in the inflammatory Offprint requests to: Dr. Veit Krenn, MD., Institute for Pathology, University of Wurzburg. Josef-Schneider-Str. 2, 0-97080 Wurzburg, Germany. Fax: +49931 2013440. e-mail : path119@mail.uniwuerzburg.de process of rheumatoid arthritis. Therefore, the analysis of synovial B-cell hybridomas and experimental expression of synovial IgYH and IgYL genes will help to characterise the antigens responsible for the pathogenesis of rheumatoid arthritis.
Open Access
Macrophages in rheumatoid arthritis
(Murcia : F. Hernández, 2007) Maruotti, Nicola; Cantatore, F.P.; Crivellato, E.; Vacca, A.; Ribatti, Doménico
In rheumatoid arthritis (RA) tissue macrophages release growth factors, matrix metalloproteinases, cytokines, and chemokines. While in normal joints there is a balance between proinflammatory and anti-inflammatory cytokines, an imbalance between these inducers and inhibitors of inflammation occurs in RA, where macrophages are responsible for inducing inflammation, matrix destruction and angiogenesis.
Open Access
Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature
(Murcia: F. Hernández, 2011) Spina, Donatella; Ambrosio, Maria Raffaella; Rocca, Bruno Jim; Di Mari, Nicoletta; Onorati, Mónica; Luzzi, Luca; Monciatti, Irene; Tosi, Piero
An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.
Open Access
Sodium transport systems in human chondrocytes Morphological and functional expression of the Na+,K+-ATPase a and D subunit isoforms in healthy and arthritic chondrocytes
(Murcia : F. Hernández, 1999) Trujillo, E.; Alvarez de la Rosa, D.; Mobasheri, A.; Ávila, J.; Gonzalez, T.; Martín Vasallo, P.
The chondrocyte is the cell responsible for the maintenance of the articular cartilage matrix. The negative charges of proteoglycans of the matrix draw cations, principally Na+, into the matrix to balance the negative charge distribution. The Na+,Kf -ATPase is the plasma membrane enzyme that maintains the intracellular Na+ and K+ concentrations. The enzyme is composed of an a and a l3 subunit, so far, 4 a and 3 B isoforms have been identified in mammals. Chondrocytes are sensitive to their ionic and osmotic environment and are capable of adaptive responses to ionic environmental perturbations particularly changes to extracellular [Na+]. In this article we show that human fetal and adult chondrocytes express three a ( a l , a 2 and the neural form of a3) and the three l3 isoforms (131, l32 and 83) of the Na+,K+-ATPase. The presence of multiple Na+,K+-ATPase isoforms in the plasma membrane of chondrocytes suggests a variety of kinetic properties that reflects a cartilage specific and very fine specialization in order to maintain the Na+/K+ gradients. Changes in the ionic and osmotic environment of chondrocytes occur in osteoarthritis and rheumatoid arthritis as result of tissue hydration and proteoglycan loss leading to a fall in tissue Na+ and K+ content. Although the expression levels and cellular distribution of the proteins tested do not vary, we detect changes in p-nitrophenylphosphatase activity "in situ" between control and pathological samples. This change in the sodium pump enzymatic activity suggests that the chondrocyte responds to these cationic environmental changes with a variation of the active isozyme types present in the plasma membrane.
Open Access
Sodium transport systems in human chondrocytes II. Expression of ENaC, Na+ K+ 2CI- cotransporter and Na+ H+ exchangers in healthy
(Murcia : F. Hernández, 1999) Trujillo, E.; Alvarez de la Rosa, D.; Mobasheri, A.; Gonzalez, T.; Canessa, C.M.; Martín Vasallo, P.
In this article, the second of two, we continue our studies of sodium-dependent transport systems in human cartilage from healthy individuals and with osteoarthritis (OA) and rheumatoid arthritis (RA). We demonstrate the presence of the epithelia1 sodium channel (ENaC), previously undescribed in chondrocytes. This system is composed of three subunits, a, 13 and y. We have shown that the human chondrocytes express at least the a and the l3 subunit of ENaC. The expression of these subunits is altered in arthritic chondrocytes. In RA samples the quantity of a and B is significantly higher than in control samples. On the other hand, ENaC a and B subunits are absent in the chondrocytes of OA cartilage. Human chondrocytes also possess three isoforms of the Na+/H+ exchanger (NHE), NHE1, NHE2 and NHE3. The NHE system is composed of a single protein and is believed to participate in intracellular pH regulation. Furthermore, our studies indicate that at least one isoform of the electroneutral Naf/K+/2C1- cotransporter (NKCC) is present in human chondrocytes. There are no obvious variations in the relative expression of NHE isoforms or NKCC between healthy and arthritic cartilage. Our data suggests that chondrocytes from arthritic cartilage may adapt to changes in their environmental sodium concentration through variations in ENaC protein levels. ENaC is also likely to serve as a major sodium entry mechanism, a process that, along with cytoskeletal proteins, may be part of mechanotransduction in cartilage.
Open Access
The role of the angiogenic molecule VEGF in the pathogenesis of rheumatoid arthritis
(Murcia : F. Hernández, 2002) Afuwape, A.O.; Kiriakidis, S.; Paleolog, E.M.
The expansion of the synovial lining of joints in rheumatoid arthritis (RA), and the subsequent invasion by the pannus of underlying cartilage and bone, necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation - ‘angiogenesis’ - is now recognised as a key event in the formation and maintenance of the pannus in RA. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, the potent pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been demonstrated to have a central involvement in the angiogenic process in RA. The additional activity of VEGF as a vascular permeability factor may also increase oedema and hence joint swelling in RA. Several studies, including those from the Kennedy Institute of Rheumatology Division, have shown that targeting angiogenesis in animal models of arthritis ameliorates disease. Inhibition of angiogenesis, as an adjunct to existing therapy of RA, or even as a stand-alone treatment, would not only prevent delivery of nutrients to the synovium, but could also lead to vessel regression and possibly reversal of disease.

Browsing by Subject "Rheumatoid arthritis"

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