Synovium, rheumatoid

In support of the concept of a cytokine dysequili-brium within the chronic inflammatory situation in rheumatoid synovium is the observation that multiple... 

Despite their short half-lives, it is possible to detect free radicals in biological tissues by the addition of nonradicals such as nitrones or nitroso compounds, which act as spin traps by forming relatively stable free radicals on reaction with the endogenous radical species. Utilizing the technique of electron spin resonance (e.s.r.) spectroscopy, we have demonstrated ROM generation by human rheumatoid synovium when subjected to cycles of hypoxia/normoxia in vitro. Using 3,5-dibromo-4-nitroso-benzenesulphonate (DBNBS) as a spin trap, a... 

In collaboration with PA Baeuerle (Freibuig), active NF-xB has been detected immunohistochemically in rheumatoid synovium by using a polyclonal antibody directed against the Rel-A NLS subunit of NF-xB (M.L. Kus, unpublished observations). The antibody employed in these studies was considered to be activity specific because IxB sterically masks the NLS sequence. NF-xB activation by ROM in the rheumatoid joint may orchestrate some of the chronic inflammatory processes characteristic of this disease. It is plausible that lL-1 and TNFo generated in the inflamed synovium as well as the up-regulated expression of adhesion molecules may be under the influence of NF-xB. 

It is unlikely that the damaging effects of ox-LDL are relevant only to the walls of blood vessels and there is no reason to suppose they are confined to one disease. The initial histopathologjcal sign of coronary heart disease is the appearance of the fetty streak on the luminal surfece of arteries. Fatty streaks are composed of aggregated macrophages that have taken up ox-LDL via the scavenger receptor. Recently, we have detected such foam cells in the rheumatoid synovium (Section 5.5). 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

AOSD, adult onset Still disease AS, ankylosing spondylitis CA, crystal-induced arthritis ERA, enthesitis-related arthritis JA, juvenile arthritis PA, psoriatic arthritis RA, rheumatoid arthritis SE, synovium explants SLE, systemic lupus erythematosus SPCIA, solid phase 2 site chemiluminescent immunometric assay RP, relapsing polychondritis. 

Page G, Lebecque S, Miossec P. Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ correlation with selective chemokine expression in rheumatoid synovium. J Immunol 2002 168(10) 5333-5341. 

Patel DD, Zachariah JP, Whichard LP. CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol 2001 98(1) 39 45. 

Middleton J, Americh L, Gayon R, et al. Endothelial cell phenotypes in the rheumatoid synovium activated, angiogenic, apoptotic and leaky. Arthritis Res Ther 2004 6(2) 60-72. 

Page G, Miossec P. Paired synovium and lymph nodes from rheumatoid arthritis patients differ in dendritic cell and chemokine expression. J Pathol 2004 204(1) 28-38. 

Watanabe N, Ando K, Yoshida S, et al. Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium. Biochem Biophys Res Commun 2002 294(5) 1121-1129. 

Nanki T, Hayashida K, El-Gabalawy HS, et al. Stromal cell-derived factor-l-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium. J Immunol 2000 165(11) 6590-6598. 

Nanki T, Imai T, Nagasaka K, et al. Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis. Arthritis Rheum 2002 46(ll) 2878-2883. 

Articulated joints between bones, for example at the knee, are covered in a capsule enclosing a space, which contains synovial fluid. The lining of the capsule is composed by the synovial membrane it is this synovium that becomes inflamed in rheumatoid arthritis (RA). Secretions produced by inflammatory cells (lymphocytes, macrophages... 

Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. Cytokine 2000 12 1092-1099. 

Rheumatoid arthritis (RA) is an inflammatory disease of the synovium which results in erosion, deformity and finally the destruction of joints. Inflammation of the joints is associated with a villous hypertrophy of the synovial membrane, which on microscopy shows proliferation of the lining layer with an inflammatory infiltrate. There is extensive expression of HLA-... 

In many chronic inflammatory diseases, angiogenesis can be identified in the inflamed lesions. For example, in rheumatoid arthritis extensive neovascularization is present in the inflamed synovium where it is one of the earliest histopathological findings [36]. Since in RA synoviocytes exhibit characteristics of tumour cells, including somatic mutations in key regulatory genes such as H-ras and the p53 tumour suppressor, RA can be viewed as a multicentric tumour-like mass that invades and destroys its local environment [37]. Concurrent increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. 

In rheumatoid arthritis, immune complexes are deposited in the affected joints, causing an inflammatory response that is amplified by eicosanoids. Lymphocytes and macrophages accumulate in the synovium, whereas leukocytes localize mainly in the synovial fluid. The major eicosanoids produced by leukocytes are leukotrienes, which facilitate T-cell proliferation and act as chemoattractants. Human macrophages synthesize the COX products PGE2 and TXA2 and large amounts of leukotrienes. 

Fishman P (2008) Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis data from a phase II clinical trial. J Rheumatol 35(1 ) 41—48 Sizova L (2008) Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheumatic drugs. Br J Clin Pharmacol 66(2) 173-178 Spargo LD, Cleland LG, Cockshell MP, Mayrhofer G (2006) Recruitment and proliferation of CD4+ T cells in synovium following adoptive transfer of adjuvant-induced arthritis. Int Immunol 18(6) 897-910... 

IL-18 augments T- and NK-cell maturation, cytotoxicity and cytokine production. It stimulates TH differentiation, promotes secretion of TNF-a, IFN-y and GM-CSF and enhances NK cell cytotoxicity by increasing FasL expression. IL-8-mediated neutrophil chemotaxis is promoted by IL-18 via its effects on TNF-a and IFN-y, which are stimulatory in action. It plays an important role in maintaining synovial inflammation and inducing joint destruction in rheumatoid arthritis. In synovium of patients with rheumatoid arthritis, enhanced levels of TNF-a and IL-1 are associated with augmented expression of IL-18. 

Lee, S.K., Bridges, S.L., Jr., Koopman, W.J., Schroeder, H.W., Jr. (1992). The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis. Arthritis Rheum. 35,905-913. 

Cl. Chabaud, M., Lubberts, E., Joosten, L., van Den Berg, W., and Miossec, P., IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. 

Gil. Gilliand, B. C., Ford, D. K., and Mannik, M., Synthesis by an established lymphocyte cell line from a rheumatoid synovium. Arthritis Rheum. 21, 330-336 (1978). 

Stevens CR, Blake DR, Merry P, Revell PA, Levick JR. A comparative study by morphometry of the microvasculature in normal and rheumatoid synovium. Arthritis Rheum 1991 34 1508-1513. 

Mapp PI, Kidd BL, Gibson SJ, Terry JM, Revell PA, Ibrahim NB, et al. Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis. Neuroscience 1990 37 143-153. 

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