Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Dai, H.; Guzman, J; Costabel, U.

doi:10.1034/j.1399-3003.1999.13f35.x

Cited by 6 publications

(9 citation statements)

References 46 publications

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“…Expression of CD120a is higher on AMs from patients suffering from sarcoidosis compared with controls. 64 The point that TNF can be detected by enzyme-linked immunosorbent assay (ELISA) although TNF activity was lacking using bioassays and the cachectin activity of TNF is not seen in sarcoidosis stimulated the search for TNF inhibitors in sarcoidosis. In fact, both TNFRs are shed from cell surfaces by metalloproteinases and can be detected as soluble molecules binding TNF and inhibiting its biological activities.…”

Section: Antigen-presenting Cellsmentioning

confidence: 99%

Sarcoidosis-Immunopathogenetic Concepts

Zissel

Prasse

Müller–Quernheim

2007

Semin Respir Crit Care Med

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Sarcoidosis is a chronic granulomatous disorder characterized by an accumulation of activated lymphocytes, predominantly T helper cells, expressing the Th1 phenotype and macrophages at sites of disease activity. Although the cause of sarcoidosis has not been elucidated, several lines of evidence suggest that granuloma formation results from exposure to one or more antigens, eliciting a T lymphocyte response. The induction and evolution of granuloma formation results from a complex interplay between diverse cell types, cytokines, and chemokines. Genetic polymorphisms may influence the clinical expression of the granuloma formation and disease outcome. This article discusses in depth the key cellular elements and signals that generate and orchestrate the sarcoid granulomatous response. The precise factors inciting the sarcoid granulomatous response have not yet been identified, but chronic exposure to microbial agents, their products, or inorganic substances may be important in the pathogenesis.

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Section: Antigen-presenting Cellsmentioning

confidence: 99%

Sarcoidosis-Immunopathogenetic Concepts

Zissel

Prasse

Müller–Quernheim

2007

Semin Respir Crit Care Med

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“…TNF‐α and other ligands of the TNF superfamily (TNF‐L) have a conflicting role in modulating apoptotic mechanisms at sites of inflammation. Some data suggest that the chronic overexpression of TNF‐α and IFN‐γ and the dysregulation of TNF‐R/TNF‐L set the stage for the persistence and the progression of the inflammatory events in ILD ( 83–85); in some circumstances, the alteration of the TNF‐R/TNF‐L balance leads to the chronic recruitment of inflammatory cells that, once in the inflamed tissue, assemble granulomatous structures. On the other hand, it has been shown that TNF‐α is induced in inflammatory cells during the resolution phase of the granulomatous process, suggesting a role for the cytokine in recovery from the disease.…”

Section: The Cytokine Network In Ildsmentioning

confidence: 99%

Immune mechanisms in interstitial lung diseases

Semenzato

Adami

Maschio

et al. 2000

Allergy

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“…In sarcoid cells, there is an increase in Fas and TNFR expression [8]. As these two molecules are death receptors that lead to apoptosis, the mechanism that protects the granuloma from apoptosis must act by inhibiting apoptosis mediated through these receptors.…”

Section: Resultsmentioning

confidence: 99%

“…In the immune system, the Fas antigen and ligand are involved in the down-regulation of immune reactions by inducing apoptosis [6,7]. The expression of the apoptosis signaling receptors, tumor necrosis factor receptor (TNFR)I and Fas, is increased on alveolar macrophages in sarcoidosis [8], and very few apoptotic cells are found in acute sarcoid granulomas, despite heavy immune cell infiltration [9 -11]. By contrast, apoptotic cells are observed in other lung diseases such as interstitial pneumonia associated with collagen vascular diseases or idiopathic pulmonary fibrosis but not in sarcoidosis [9].…”

Section: Introductionmentioning

confidence: 99%

High expression of p21Waf1 in sarcoid granulomas: a putative role for long-lasting inflammation

Xaus

Besalduch

Comalada

et al. 2003

Journal of Leukocyte Biology

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In sarcoid granulomas, apoptotic events are reduced, which explains their characteristic long-lasting inflammation. We have described that interferon-gamma (IFN-gamma) inhibits apoptosis in macrophages through the expression of p21(Waf1). Here, we explore the molecular mechanisms involved in the inhibition of apoptosis in sarcoid granulomas. We analyzed skin biopsies from 19 sarcoidosis patients and 16 controls. Total RNA was subjected to semiquantitative reverse transcriptase-polymerase chain reaction analysis. There was no difference found in the expression of proapoptotic (Bax and Bcl-X(s)) or antiapoptotic (Bcl-2 and Bcl-X(L)) genes nor in the expression of the tumor suppressor gene p53. Furthermore, the expression of IFN-gamma and the cdk inhibitors p21(Waf1) and p27(Kip1) were analyzed. IFN-gamma was detected in 37% of the sarcoidosis patients, and controls were negative (P<0.02). In addition, a higher proportion of patients expressing p21(Waf1) (58%) versus controls (12%) was found (P<0.005). There was a significant correlation between the expression of IFN-gamma and p21(Waf1) (r=0.69) and between p21(Waf1) and fibronectin (r=0.65). Finally, using immunohistochemistry, high p21(Waf1) reactivity was observed inside the granuloma. We conclude that the high levels of p21(Waf1) in sarcoidosis may explain the absence of apoptosis in the granuloma and the persistence of inflammation.

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Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Cited by 6 publications

References 46 publications

Sarcoidosis-Immunopathogenetic Concepts

Sarcoidosis-Immunopathogenetic Concepts

Immune mechanisms in interstitial lung diseases

High expression of p21Waf1 in sarcoid granulomas: a putative role for long-lasting inflammation

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