Identification of the advanced glycation end products N(epsilon)-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis.

BACKGROUND: Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found. OBJECTIVE: To determine the presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology. METHODS: Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. RESULTS: CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA. CONCLUSIONS: CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response.

Expression of cell adhesion molecules and cytokines in murine antigen-induced arthritis.

Adhesion molecules and cytokines are important in chronic inflammatory conditions such as rheumatoid arthritis (RA) by virtue of their role in cell activation and emigration. Using immunohistochemical techniques we studied the expression of adhesion molecules and cytokines in cryopreserved sections of murine knee joint in the course of antigen-induced arthritis, an animal model of human RA. Various adhesion molecules and cytokines are expressed in the arthritic joint tissue. LFA-1, Mac-1, CD44, ICAM-1 and P-selectin were strongly expressed in the acute phase and to a lesser degree in the chronic phase of arthritis. VLA-4 and VCAM-1 appeared to be moderately expressed on day 1, L-selectin between days 1 and 3. LFA-1, Mac-1, CD44, alpha 4-integrin, ICAM-1 and the selectins were found expressed on cells of the synovial infiltrate, LFA-1, Mac-1 and ICAM-1 on the synovial lining layer, and VCAM-1 and P-selectin on endothelial cells. Expression of E-selectin could be demonstrated throughout the experiment at a low level in cells of the acute cell infiltrate. Cytokines, especially IL-2, IL-4, IL-6, TNF, and IFN-gamma, were heavily expressed during the acute phase of arthritis in cellular infiltrate. Taken together these data demonstrate that cytokines and their activation of adhesion molecules contribute to cell infiltration and activation during the initial phase of arthritis and to the induction and progression of tissue destruction in arthritic joints. These molecules might be potential targets for novel therapeutic strategies in inflammatory and arthritic disorders.

[Argyria. A clinical, chemical analytic and micromorphologic study]. / Zur Frage der Argyrie. Eine klinische, analytisch-chemische und mikromorphologische Untersuchung.

A 62-year-old male patient developed generalized argyria following the intake of silver-proteinacetyltannate (Targesin; approx. 60 g in 10 years) as treatment for gastric discomfort. On histological and ultrastructural examination of the skin, silver particles were found not only in the usual locations but also in the Schwann cell, the mast cell, and in smooth muscle cells. This corresponded to chemical analysis, proving the presence of this metal in the skin. In the blood, a level of 0.26 +/- 0.04 ppm silver was found. By means of an equation, attempts were made to demonstrate the reaction process involved in the formation of Ag2S as subjected to the photochemical effect of sunlight.