Possible clearance of effete polymorphonuclear leucocytes from synovial fluid by cytophagocytic mononuclear cells: implications for pathogenesis and chronicity in inflammatory arthritis.

Jones, Sian; Denton, J.; Holt, P J; Freemont, A. J.

doi:10.1136/ard.52.2.121

Cited by 32 publications

(13 citation statements)

References 23 publications

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“…This is a characteristic which appears early in apoptosis and is used as a structure for recognition by certain phagocytes (31,33); yet this also failed to show any positive T cells in synovial fluid of RA patients. Furthermore, the high prevalence of apoptotic neutrophils in the synovium, which has been reported previously (34) and was also observed in this study, suggests that failure to identify apoptotic cells before phagocytosis is unlikely, because these cells are also cleared by macrophages and the recognition mechanisms are the same (31,32). Perhaps the most intriguing observation in this respect was that patients with crystal arthritis consistently showed evidence of high levels of T cell apoptosis in vivo.…”

Section: Discussionsupporting

confidence: 52%

Inhibition of T cell apoptosis in the rheumatoid synovium.

Salmon¹,

Scheel‐Toellner²,

Huissoon³

et al. 1997

J. Clin. Invest.

262

241

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Section: Discussionsupporting

confidence: 52%

Inhibition of T cell apoptosis in the rheumatoid synovium.

Salmon¹,

Scheel‐Toellner²,

Huissoon³

et al. 1997

J. Clin. Invest.

262

241

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“…26 Furthermore, clearance of apoptotic neutrophils from the synovial fluid has been suggested to be crucial to joint inflammation because dying neutrophils may help sustain the inflammatory response. 2,54 AP214 produced promising results with respect to disease incidence, paw volume, and disease score, which were significantly reduced at the low dose of 400 g/kg. In contrast to the results produced in the peritonitis model, AP214 was inactive at 800 g/kg, a finding that may be related to the down-regulation of MC receptors discussed previously, because the compound was given twice daily over a 10-day regimen.…”

Section: Discussionmentioning

confidence: 98%

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

Montero‐Melendez

Patel

Seed

et al. 2011

The American Journal of Pathology

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Synthetic and natural melanocortin (MC) peptides afford inhibitory properties in inflammation and tissue injury, but characterization of receptor involvement is still elusive. We used the agonist AP214 to test MC-dependent anti-inflammatory effects. In zymosan peritonitis, treatment of mice with AP214 (400 to 800 g/kg) inhibited cell infiltration, an effect retained in MC receptor type 1, or MC 1 , mutant mice but lost in MC 3 null mice. In vitro, cytokine release from zymosan-stimulated macrophages was affected by AP214, with approximately 80%, 30%, and 40% reduction in IL-1␤, tumor necrosis factor-␣, and IL-6, respectively. Inhibition of IL-1␤ release was retained in MC 1 mutant cells but was lost in MC 3 null cells. Furthermore, AP214 augmented uptake of zymosan particles and human apoptotic neutrophils by wild-type macrophages: this proresolving property was lost in MC 3 null macrophages. AP214 displayed its pro-efferocytotic effect also in vivo.

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“…Previous reports have focused on neutrophil apoptosis in synovial fluid ( 15 ), and cells in inflammatory joint effusions show morphologic features of PCD (16). However, the reason for synovial hyperplasia, a characteristic change in rheumatoid arthritis joint tissues, and its relation to apoptosis is obscure.…”

Section: Introductionmentioning

confidence: 99%

“…The DNA pellet was resuspended in Tris-EDTA buffer. [5][6][7][8][9][10][11][12][13][14][15] ,g of DNA from each sample was subjected to electrophoresis on 1.5% agarose gel containing ethidium bromide and visualized under UV illumination.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in rheumatoid arthritis synovium.

Firestein

Yeo²,

Zvaifler³

1995

J. Clin. Invest.

355

249

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RA synovial tissue (ST) was studied to determine if and where apoptosis occurs in situ. Genomic DNA was extracted from 5 RA and 1 osteoarthritis ST samples. Agarose gel electrophoresis demonstrated DNA ladders characteristic for apoptosis from each tissue. In situ end labeling (ISEL) was used to identify DNA strand breaks consistent with apoptosis in frozen sections. 12 RA and 4 osteoarthritis ST were studied by ISEL and all were positive, but only 2 of 4 normal tissues were positive. The primary location of apoptotic cells was the synovial lining. Some sublining cells were also positive, but lymphoid aggregate staining was conspicuously absent. Immunohistochemistry and ISEL were combined and showed that the lining cells with DNA strand breaks were mainly macrophages, although some fibroblastlike cells were also labeled. Sublining cells with fragmented DNA included macrophages and fibroblasts, but T cells in lymphoid aggregates, which expressed large amounts of bcl-2, were spared. DNA strand breaks in cultured fibroblastlike synoviocytes was assessed using ISEL. Apoptosis could be induced by actinomycin D, anti-fas antibody, IL-1, and TNF-a but not by IFN-y. Fas expression was also detected on fibroblast-like synoviocytes using flow cytometry. Therefore, DNA strand breaks occur in synovium of patients with arthritis. Cytokines regulate this process, and the cytokine profile in RA (high IL-1/TNF; low IFN-y) along with local oxidant injury might favor induction of apoptosis. (J. Clin. Invest. 1995.96:1631-1638

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Possible clearance of effete polymorphonuclear leucocytes from synovial fluid by cytophagocytic mononuclear cells: implications for pathogenesis and chronicity in inflammatory arthritis.

Abstract: (Ann Rheum Dis 1993; 52: 121-126)

Cited by 32 publications

References 23 publications

Inhibition of T cell apoptosis in the rheumatoid synovium.

Inhibition of T cell apoptosis in the rheumatoid synovium.

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

Apoptosis in rheumatoid arthritis synovium.

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