scholarly journals Activation of neutrophil reactive-oxidant production by synovial fluid from patients with inflammatory joint disease. Soluble and insoluble immunoglobulin aggregates activate different pathways in primed and unprimed cells

1992 ◽  
Vol 286 (2) ◽  
pp. 345-351 ◽  
Author(s):  
J Robinson ◽  
F Watson ◽  
R C Bucknall ◽  
S W Edwards
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Oxidase Activity ◽  
Soluble Fraction ◽  
Protein A ◽  
Joint Disease ◽  
Human Neutrophils ◽  
Synovial Fluids ◽  
Transient Activity ◽  
Reactive Oxidant

Cell-free synovial fluid from patients with rheumatoid arthritis stimulated the NADPH oxidase activity in human neutrophils, which reached a peak 15-20 min after addition. Insoluble immunoglobulin aggregates isolated from these fluids activated a similar pattern of oxidase activity. However, when synovial fluid was added to neutrophil suspensions which had been previously exposed to granulocyte-macrophage colony-stimulating factor, the stimulated oxidase activity was biphasic, in that an additional transient activity was observed which reached a peak within 5 min of addition. The additional neutrophil-stimulating activity could not be sedimented by centrifugation at 330,000 g-min, and only activated oxidase activity in neutrophils which had previously been primed. The neutrophil-stimulating activity in this soluble fraction was removed by Protein A affinity chromatography, and activity was recovered in eluates from this column. Thus activity in this soluble fraction from synovial fluid is attributed to the presence of soluble immunoglobulin aggregates. Whereas oxidase activity stimulated by the isoluble immunoglobulin aggregates was inhibited by staurosporine (and hence largely dependent on the activity of protein kinase C), the activity stimulated by the soluble immunoglobulin aggregates was staurosporine-insensitive. The soluble immunoglobulin aggregates were present at significantly higher levels in synovial fluids from patients with rheumatoid arthritis compared with those from other joint arthropathies. Thus rheumatoid synovial fluids possess heterogeneous immunoglobulin aggregates which activate neutrophils via distinct molecular pathways. As neutrophils within rheumatoid joints are primed, the soluble immunoglobulin aggregates are likely to be of importance in disease pathology.

scholarly journals Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Cecilia Machado Diaz ◽  
Araceli Chico Capote ◽  
Celia Aurora Arrieta Aguero ◽  
Yunier Rodríguez Alvarez ◽  
Diana García del Barco Herrera ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reverse Signaling ◽  
Synovial Fluids ◽  
Inflammatory Processes ◽  
Membrane Bound ◽  
Interleukin 15 ◽  
Interleukin 15 Receptor Alpha ◽  
Pro Inflammatory Cytokines

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

scholarly journals Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthritis synovial fluids

2000 ◽  
Vol 120 (1) ◽  
pp. 183-187 ◽  
Author(s):  
P. K. E. Trinder ◽  
T. P. Hickling ◽  
R. B. Sim ◽  
D. Brackertz ◽  
M. Loos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Synovial Fluids

Expression and activity profiling of selected cysteine cathepsins and matrix metalloproteinases in synovial fluids from patients with rheumatoid arthritis and osteoarthritis

2010 ◽  
Vol 391 (5) ◽  
pp. 571-579 ◽  
Author(s):  
Urška Požgan ◽  
Dejan Caglič ◽  
Blaž Rozman ◽  
Hideaki Nagase ◽  
Vito Turk ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Critical Role ◽  
Detailed Comparison ◽  
Matrix Metalloproteases ◽  
Cathepsin S ◽  
Cysteine Cathepsins ◽  
Synovial Fluids ◽  
Expression And Activity ◽  
Stimulation Of

Abstract Cysteine cathepsins and matrix metalloproteases are considered to play important roles in the development of arthritic diseases. Their accumulation in synovial fluid of primarily rheumatoid arthritis patients is also well documented. However, a detailed comparison between the protease levels and activities between rheumatoid arthritis samples and osteoarthritis samples has never been made. Here, we report that both cysteine cathepsins B and S and matrix metalloproteases-1, -3 and -13 are detected in patient synovial fluid samples with significantly higher levels detected in rheumatoid arthritis patients. Among the proteases, cathepsin S was found to be significantly elevated, consistent with its critical role in the immune response. These results suggest that cysteine cathepsins have a major role in inflammation at least in rheumatoid arthritis. In addition to proteases, interleukin-6 was detected at significant levels in most samples, suggesting that proinflammatory cytokines might be in-volved in the stimulation of expression of these proteases during inflammation.

Endothelin-1 Production by Human Synoviocytes

1998 ◽  
Vol 35 (2) ◽  
pp. 290-294 ◽  
Author(s):  
Hiroshi Yoshida ◽  
Yuji Imafuku ◽  
Morihiro Ohhara ◽  
Masayuki Miyata ◽  
Reji Kasukawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Arthritis ◽  
Synovial Cells ◽  
Type B ◽  
Serum Samples ◽  
Synovial Macrophage ◽  
Significant Difference ◽  
Synovial Fluids ◽  
Synovial Tissues

Immunoreactive (ir)-endothelin (ET)-l concentrations in serum samples and synovial fluids from patients with rheumatoid arthritis were higher than concentrations in sera obtained from healthy volunteers. No significant difference in ir-ET-1 concentrations in synovial fluid was observed between rheumatoid arthritis patients and osteoarthritis patients. Cultured fluids of synovial cells collected from synovial tissues and leucocytes from synovial fluids of rheumatoid arthritis patients were studied to determine the origin of ir-ET-1 in synovial fluids. Ir-ET-1 was detected in the cultured fluids of synovial macrophage-like type A cells, but not in those of fibroblast-like type B cells from the synovial tissues or leucocytes from the synovial fluids. Longitudinal studies showed that the ir-ET-1 concentration in the cultured fluid reached a peak around 24 h after starting the culture. ET-1 secreted from macrophage-like synoviocytes may be involved in the pathogenesis of inflammatory arthritis.

Increased Levels of Interleukin 33 in Sera and Synovial Fluid from Patients with Active Rheumatoid Arthritis

2009 ◽  
Vol 37 (1) ◽  
pp. 18-25 ◽  
Author(s):  
YASUSHI MATSUYAMA ◽  
HITOAKI OKAZAKI ◽  
HIROYUKI TAMEMOTO ◽  
HIROTAKA KIMURA ◽  
YASUYUKI KAMATA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Sandwich Elisa ◽  
Protein A ◽  
Peripheral Blood Mononuclear ◽  
Interleukin 33 ◽  
Activity Group ◽  
Culture Supernatants

Objective.To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33.Methods.Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1ß and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting.Results.Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS.Conclusion.IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA.

scholarly journals FRI0002 S100A11 (CALGIZZARIN) IS RELEASED DURING NEUTROPHIL EXTRACELLULAR TRAPS FORMATION AND STIMULATES RELEASE OF IL-6 AND TNF IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 572.3-572
Author(s):  
A. Navratilova ◽  
V. Becvar ◽  
J. Baloun ◽  
D. Damgaard ◽  
C. H. Nielsen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Response ◽  
Synovial Tissue ◽  
Inflammatory Responses ◽  
Protein A ◽  
Neutrophil Extracellular Traps ◽  
Immunofluorescence Staining ◽  
Extracellular Traps ◽  
Healthy Donors

Background:S100A11 protein, a member of S100 family, has been associated with several autoimmune inflammatory conditions such as rheumatoid arthritis (RA). Although the pathogenesis of autoimmune diseases is not fully understood, the formation of neutrophil extracellular traps (NETs) seems to play a certain role. Recent data indicate that S100A8/A9 is released via NETosis and can further augment inflammatory responses.Objectives:The aim of our study was to examine the association of S100A11 with NETs in RA.Methods:To assess the expression of S100A11 by neutrophils of RA synovial tissue (n=8), immunofluorescence staining of S100A11 and myeloperoxidase (MPO) was performed. The levels of S100A11 and MPO in RA synovial fluid (n=23) were measured by ELISAs (RayBiotech and Abcam), and the activity of peptidyl arginine deiminases (PADs) was measured by an in-house immunoassay. NETosis was induced by adding phorbol 12-myristate 13-acetate (PMA) to neutrophils from RA patients (n=7). Release of NETs was visualised by immunocytochemistry (n=7) and the presence of S100A11 in supernatants was analysed by ELISA (RayBiotech). Neutrophils purified from healthy donors (n=5) were stimulated by S100A11 and the release of cytokines TNF and IL-6 was measured by ELISA (RayBiotech).Results:S100A11 was expressed by synovial tissue neutrophils of the RA patients (n=8). The levels of S100A11 in the synovial fluid of RA patients (n=23) correlated with the levels of a NETosis marker MPO (r=0.562, p=0.005) and with PADs activity (r=0.690, p<0.001), which affects NETs immunogenicity. Neutrophils treated with LPS (n=7) did not up-regulate the secretion of S100A11 compared to unstimulated controls (0.23±0.05 vs. 0.29±0.07 ng/ml; p=ns). However, the release of S100A11 was markedly up-regulated in PMA-stimulated neutrophils undergoing NETosis compared to untreated controls (1.16±0.17 vs. 0.29±0.07 ng/ml; p<0.001). Moreover, diphenyleneiodoinum treatment abolished PMA-induced S100A11 secretion. By immunofluorescence staining (n=8) we demonstrated that neutrophils activated by PMA release NETs containing S100A11 protein. In addition, extracellular S100A11 augmented the inflammatory response of neutrophils from healthy donors (n=5) via IL-6 and TNF in comparison with unstimulated cells (0.39±0.11 vs. 0.05±0.01 pg/ml; p<0.05 and 0.31±0.06 vs. 0.09±0.03 pg/ml; p<0.05).Conclusion:Here we show for the first time that release of S100A11 by neutrophils is dependent on NETosis. Moreover, extracellular S100A11 augments the inflammatory response by inducing TNF and IL-6 secretion in neutrophils.Acknowledgments:Supported by MHCR 023728Disclosure of Interests:Adela Navratilova: None declared, Viktor Becvar: None declared, Jiří Baloun: None declared, Dres Damgaard: None declared, Claus Henrik Nielsen: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Lucie Andres Cerezo: None declared, David Veigl: None declared

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