Cells In Synovial Tissue Research Articles

Immunoreactive alpha 2-macroglobulin in rheumatoid synovial membrane.

alpha 2-Macroglobulin was demonstrated immunohistochemically in macrophage-like cells of rheumatoid arthritic synovial tissue. It is concluded that these intracellular deposits probably represent phagocytosed protease-alpha 2-macroglobulin complexes. A contributing local production of alpha 2-macroglobulin is, however, not excluded by the present findings.

Ia+ T cells in synovial fluid and tissues of patients with rheumatoid arthritis.

Markedly elevated levels of T cells expressing Ia antigens were found in the synovial membranes and synovial fluids of patients with rheumatoid arthritis. The primary increase in expression of the Ia antigens was on the OKT 8+ (suppressor/cytotoxic) T cell subset. In addition, the total percentage of OKT 8+ T cells in intraarticular sites was usually greater than levels in peripheral blood. Small numbers of OKT 4+ (helper/inducer) cells bearing Ia antigens were also identified. The characteristic increase in the Ia+ T cells in peripheral blood was not encountered in most patients treated with D-penicillamine.

Appearance of anti-HLA-DR-reactive cells in normal and rheumatoid synovial tissue.

The reactivity of rabbit anti-HLA-DR antigen antibodies with cells in normal and rheumatoid synovial tissue was investigated by indirect immunofluorescence on frozen sections of tissue. The antibodies reacted with a significant proportion of the synovial lining cells of both normal and rheumatoid synovial tissue, with endothelial cells, and with a number of, most probably, migratory cells. After dispersion of cells from rheumatoid synovial tissue by digestion with collagenase and DNase, adherent cells of both a macrophage-like and a dendritic appearance reacted with the anti-HLA-DR antigen antibodies. The adherent cells were also found to be potent stimulators in the allogeneic MLR. In addition, it was found that a high percentage of T lymphocytes from both peripheral blood and synovial tissue of rheumatoid patients bound anti-HLA-DR antibodies. The present data suggest a role for synovial lining cells in HLA-D-locus-dependent events of importance in the pathogenesis of rheumatoid arthritis and other joint diseases and point to the need for further investigations on T lymphocytes derived from the site of inflammation in the study of rheumatoid arthritis.

Effect of inflammatory arthritis on dexamethasone receptors in phagocytes--a possible role for plasma factors.

Synovial tissue cells from patients with seropositive rheumatoid arthritis bind dexamethasone in a similar fashion to the classical steroid receptors on other cells. In contrast, synovial fluid cells and blood PMNLs from these patients bind dexamethasone with much reduced affinity. Some component of plasma may interfere with the binding of dexamethasone to its receptor.

Connective tissue activation. XVII. Radioimmunoassay of a human platelet derived connective tissue activating peptide (CTAP-III) and specificities of anti-CTAP-III sera

The platelet-derived connective tissue activating peptide (CTAP-III) has been shown to be an important factor stimulating the metabolism and proliferation of human connective tissue cell strains, including synovial tissue cells. The quantities of CTAP-III affecting the cellular changes and the amounts in various biologic fluids and tissues are small. The objectives of this study were to develop a radioimmunoassay (RIA) for CTAP-III and to ascertain the specificities of the anti-CTAP-III sera reagents. The antisera were shown not to cross-react with a number of polypeptide hormones. However, two other platelet proteins, β-thromboglobulin and low affinity platelet factor-4, competed equally as well as CTAP-III for anti-CTAP-III antibodies in the RIA system. Thus, the three platelet proteins are similar or identical with respect to those portions of the molecules constituting the reactive antigenic determinants. The levels of material in normal human platelet-free plasma that inhibited anti-CTAP-III-12S!-CTAP-III complex formation were determined to be 34 ± 13 (S.D.) ng/ml.

Pinocytosis in human synovial cells in vitro. Evidence for enhanced activity in rheumatoid arthritis.

Human synovial tissue cells in monolayer can be shown to take up and digest a soluble protein, horseradish peroxidase (HRP). Uptake of HRP was linear with increasing concentrations of substrate and cell protein and with time for up to 4 h. Low temperature (4 degrees C), and sodium fluoride, an inhibitor of glycolysis were the most effective metabolic inhibitors of endocytosis. In addition, colchicine, an inhibitor of microtubule assembly, and yeast mannan, an inhibitor of mannose-specific receptors, reduced HRP uptake. Synovial cells from patients with rheumatoid arthritis (RSC) demonstrated a statistically significantly higher rate of endocytosis (247 +/- 107 ng HRP/100 micrograms cell protein per 2 h.) than cells from control, nonrheumatoid patients (NSC) (100 +/- 80 ng HRP/100 micrograms cell protein per 2 h). Thus, it is possible to discriminate RSC from NSC by their quantitatively different rates of endocytosis. Digestion of HRP by synovial cells is statistically significant by 6 h after uptake. A faster initial rate of digestion was seen in RSC. Over the first 6--8 h of incubation 42% of the endocytosed HRP was still cell-associated in RSC and 67% remained in NSC cultures. However, by 24 h 20--30% of endocytosed HRP was found in both types of cultures. These results indicate that endocytosed molecules may accumulate more rapidly in RSC and persist within their lysosomes for a longer time than in NSC. The quantitative determination of enhanced endocytosis by RSC compared with NSC suggests that this increased activity may have a role in the pathological function of synovial tissue in rheumatoid arthritis.

Cell Proliferation in Rheumatoid Synovial Tissue

Rheumatoid synovial tissue cell proliferation was studied by incubating fresh synovial tissue samples with [3H]-thymidine in vitro. The samples were collected at operation from 7 rheumatoid patients. It was found that 0.9-4.9% of the total cell population, excluding the synovial lining cells, became labelled.

Immunoglobulins IgG and IgM in synovial fluids of swine with erysipelothrix polyarthritis

Concentrations of IgG and IgM immunoglobulins in synovial fluids and sera from a group of swine with experimentally produced Erysipelothrix rhusiopathiae polyarthritis were measured to determine if there was local synthesis of these immunoglobulins by plasma cells in arthritic synovial tissue. IgG and, to a lesser extent, IgM were significantly higher in arthritic than in nirmal synovial fluids from the same group of swine and this increase could only partly be explained by the increased permeability of the arthritic synovial membrane to plasma proteins. When synovial fluid values of IgG and IgM were calculated on the basis of companion serum concentration it was found that 82% of IgG, and 25% of IgM estimations were significantly elevated above levels in normal joints indicating that IgG was the dominant immunoglobulin synthesized.

Proliferation of synovial tissue cells in rats with adjuvant disease.

Proliferation of synovial lining cells and fibroblasts in adjuvant arthritis of rats was investigated by autradiographic methods. As manifestation of the generalized experimental disease increased labelling rates of both cell types were found in all joints. While in the knee joint this cellular proliferation was of a short duration, it progressed in the ankle joint until the joints were destroyed. It is concluded that increased cellular proliferation is an important mechanism leading to joint destruction in adjuvant arthritis.

The Effect of Experimentally Induced Redox Changes on Human Rheumatoid and Non-Rheumatoid Synovial Tissue in vitro

This study has confirmed that the lysosomal membranes in the synovial lining cells of human rheumatoid synovial tissue are abnormally labile; that the cytoplasmic redox balance, as measured by the proportion of dithiol to disulphide groups, is exceptionally reductive; and that there is an excessive rate of generation of reduced NADP despite little change in its rate of oxidation. These results suggested that the increased reductive conditions in the cytoplasm might contribute to the state of the lysosomes. To test this, human synovial tissue was maintained in vitro , in adult maintenance culture, and hydrogendonating or hydrogen-accepting molecules were added to the culture medium. It was shown that ascorbate acts as a hydrogen-donor. In non-rheumatoid cells it increased the proportion of cytoplasmic sulphydryl groups (which indicates a more reductive redox balance) and also increased the lability of the lysosomal membranes. Hydrogen-accepting molecules, such as dehydroascorbate and particularly menadione, produced the reverse effect. Similar effects occurred in rheumatoid synovial lining cells, in which menadione also diminished the rate of generation of NADPH. It seems likely, therefore, that redox systems in the cytoplasm and in the extra-cellular space, can influence the cytoplasmic dithiol: disulphide balance and the functional state of lysosomal membranes in synovial lining cells. In rheumatoid synovial tissue, menadione diminishes the excessively reductive conditions in these cells and stabilizes lysosomal membranes. In der vorliegenden Arbeit werden neue Hinweise aufgeführt, daß die Membranen von Lysosomen in Synoviazellen bei der rheumatoiden Arthritis des Menschen gesteigert labil sind; der Redoxquotient des Zytoplasmas gemessen am Quotienten Dithiol zu Disulfidgruppen liegt stark im Reduktiven. Reduziertes NADP wird in vermehrtem Maß gebildet, bei fast normaler Oxydationsfähigkeit. Möglicherweise bedingen die vermehrt reduktiven Kräfte im Zytoplasma den Zustand der Lysosomen. Um diese Hypothese zu überprüfen, werden menschliche Synoviazellen in vitro gehalten, Moleküle den Kulturen zugesetzt, die entweder Wasserstoffdonatoren oder Wasserstoffakzeptoren sind, z.B. Ascorbat wirkt als Wasserstoffdonator. In nichtrheumatoiden Synoviazellen erhöht es die Anzahl zytoplasmatischer Sulphydrylgruppen und steigert somit die Labilität lysosomaler Membranen in den Synoviazellen und erhöht

The morphology of the synovial tissue and articular fluid cells in rheumatoid polyarthritis--studied with the optical and electronic microscope.

SummaryThe authors have studied the morphological alterations that take place in the deep layers of diseased synovia. Fragments of synovial membrane from sixteen patients suffering from rheumatoid polyarthritis were used as well as synovial fluid from another six patients. The studies were carried out in the optical as well as in the electronic microscope. The authors conclude that the pathogenic mechanism implies that the deep, vascular layer of the synovia is the site of origin of the functional and morphological alterations. This speaks in favour of vascularitis as an element of primordial order.

"Epithelial transformation" of human synovial connective tissue cells: cytologic and biochemical consequences.

SummaryPrimary cultures of fibroblast-like cells from rheumatoid synovial tissue changed in vitro to a cell population exhibiting epithelial morphology, heteroploidy, altered growth characteristics, and decreased capacity to synthesize hyaluronic acid. Quantitative changes in the protein and nucleic acid composition of the cells were also demonstrated.