Eosinophil apoptosis and the resolution of airway inflammation in asthma.

Woolley, Karen L.; Gibson, Peter G.; Carty, Kellie; Wilson, Amanda; Twaddell, SH; Woolley, M. J.

doi:10.1164/ajrccm.154.1.8680686

Cited by 247 publications

(173 citation statements)

References 24 publications

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“…33 Asthmatic individuals show an increase in the number of eosinophils, a decrease in the expression of FasL, and a decrease in the number of apoptotic cells in the airway but not that of healthy persons. 23,34 Moreover, the number of apoptotic eosinophils is reduced within the airway of asthmatic individuals compared with patients with other eosinophilic disorders of the lung, such as chronic bronchitis. 24 During allergic airway inflammation induced by OVA in mice, FasL mRNA and protein is markedly reduced in the airway epithelium.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

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Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligandmediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-a production also decreased in AdFasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

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Section: Discussionmentioning

confidence: 99%

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

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“…Delayed apoptosis of activated granulocytes has been reported to occur in a number of inflammatory conditions in humans or animal models, 5,52 including rheumatoid arthritis, 53 acute pancreatitis, 54 bacterial pneumonia, 55 inflammatory bowel disease, 56 asthma, [57][58][59] and following surgery. 60,61 Failure of these cells to undergo programmed cell death and to be cleared by phagocytes allows persistent and inappropriate inflammation to occur, as activated granulocytes release a number of proinflammatory mediators, which may contribute significantly to the aetiology of the disease.…”

Section: In Vivo Effects Of No and Its Therapeutic Potentialmentioning

confidence: 99%

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

et al. 2003

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Apoptosis of inflammatory cells is a critical event in the resolution of inflammation, as failure to undergo this form of cell death leads to increased tissue damage and exacerbation of the inflammatory response. Many factors are able to influence the rate of apoptosis in neutrophils, eosinophils, monocytes and macrophages. Among these is the signalling molecule nitric oxide (NO), which possesses both anti-and proapoptotic properties, depending on the concentration and flux of NO, and also the source from which NO is derived. This review summarises the differential effects of NO on inflammatory cell apoptosis and outlines potential mechanisms that have been proposed to explain such actions.

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“…Cells are rapidly phagocytosed either whole or as fragments bound by an intact membrane, preventing exposure of adjacent tissues to their intracellular contents. An evolving hypothesis that the tissue load of eosinophils in allergic disorders and asthma is related to the inhibition of or defects in the apoptotic process is supported by studies that provide evidence that eosinophil clearance by apoptosisinduction has clinical relevance in asthma [3][4][5]. Therefore, this may represent a plausible target for novel therapeutic intervention.…”

mentioning

confidence: 99%

“…Examination of induced sputum using nebulised hypertonic saline is a well-validated noninvasive procedure for the assessment of airway inflammation in asthma [5][6][7][8]. However, to date there have been few studies that have utilised this technique to compare the relationship between measures of eosinophil apoptosis or survival in induced sputum with clinical and functional parameters of disease severity [5][6][7][8][9][10].…”

mentioning

confidence: 99%

“…However, to date there have been few studies that have utilised this technique to compare the relationship between measures of eosinophil apoptosis or survival in induced sputum with clinical and functional parameters of disease severity [5][6][7][8][9][10]. The authors hypothesised that there is a relationship between reduced eosinophil apoptosis and both a global clinical severity score and separate components of the asthma phenotype.…”

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confidence: 99%

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Reduced eosinophil apoptosis in induced sputum correlates with asthma severity

et al. 2003

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This study was carried out to investigate the relationship between induced sputum eosinophil apoptosis and clinical severity score, airway obstruction and symptom scores in patients with chronic stable asthma.Altogether, 41 chronic stable asthmatic subjects of varying severity defined by Aas score and 17 control subjects underwent spirometry, symptom questionnaire and successful sputum induction. Sputum was processed and cytospins prepared for light microscopy to determine normal and apoptotic eosinophils.Mild asthmatic subjects had a significantly lower percentage sputum eosinophils and a significantly higher eosinophil apoptotic ratio (AR) than moderate or chronic severe asthmatics. Severe asthmatic subjects had a significantly greater age, duration of asthma and sputum eosinophil count?mL -1 than mild asthmatic subjects. Asthmatic subjects9 symptom scores, severity scores and age inversely correlated with AR and the percentage of sputum eosinophils. Baseline forced expiratory volume in one second inversely correlated with percentage sputum eosinophils and positively correlated with AR.The study demonstrates a relationship between reduced sputum eosinophil apoptosis and increased clinical severity of chronic stable asthma, providing additional evidence that eosinophil apoptosis may be important in the resolution of eosinophilic airway inflammation in asthma. Eur Respir J 2003; 22: 484-490.

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Eosinophil apoptosis and the resolution of airway inflammation in asthma.

Cited by 247 publications

References 24 publications

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

Reduced eosinophil apoptosis in induced sputum correlates with asthma severity

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