Bcl-2 expression in sputum eosinophils in patients with acute asthma

Jang, An‐Soo; Choi, In Suck; Lee, Soong; Seo, Jeong-Pyeong; Yang, Seungwon; Park, Chang-Soo

doi:10.1136/thorax.55.5.370

Cited by 22 publications

(23 citation statements)

References 17 publications

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“…Fas expression on eosinophils of healthy and asthmatic subjects appears similar [112], but studies of patients with ragweed-allergic asthma have demonstrated increased concentrations of TRAIL 24 h after allergen challenge in asthmatic subjects as compared with controls, which correlates with airway eosinophilia [113]. There is evidence of increased expression of the anti-apoptotic protein Bcl-2 in eosinophils from sputum of patients with severe asthma [114]. Eosinophil apoptosis regulates clearance of these cells from the airway; BECs (bronchial epithelial cells) phagocytose apoptotic eosinophils [115] and treatment with glucocorticoids increases the clearance of these cells by both BECs and alveolar macrophages [113].…”

Section: Eosinophil Apoptosis In Allergic Inflammationmentioning

confidence: 97%

Granulocyte apoptosis in the pathogenesis and resolution of lung disease

et al. 2006

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Apoptosis, programmed cell death, of neutrophil and eosinophil granulocytes is a potential control point in the physiological resolution of innate immune responses. There is also increasing evidence that cellular processes of apoptosis can be dysregulated by pathogens as a mechanism of immune evasion and that delayed apoptosis, resulting in prolonged inflammatory cell survival, is important in persistence of tissue inflammation. The identification of cell-type specific pathways to apoptosis may allow the design of novel anti-inflammatory therapies or agents to augment the innate immune responses to infection. This review will explore the physiological roles of granulocyte apoptosis and their importance in infectious and non-infectious lung disease.

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Section: Eosinophil Apoptosis In Allergic Inflammationmentioning

confidence: 97%

Granulocyte apoptosis in the pathogenesis and resolution of lung disease

et al. 2006

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“…Previous reports investigating the role of Bcl-2 homologues in eosinophils have concentrated on the level of protein expression. Human peripheral blood eosinophils endogenously express relatively high levels of proapoptotic Bax and antiapoptotic Bcl-x L , with little or no detectable antiapoptotic Bcl-2 expression, 12,13 although there is some evidence of higher Bcl-2 expression in eosinophils derived from patients with asthma and hypereosinophilic syndrome, 14,15 and stimulation in vitro with IL-5 resulted in detectable up-regulation of Bcl-2 expression in some 12,16 but not all studies. 17,18 It has been proposed that susceptibility to cell death is determined by the ratio of death agonist to death antagonist and their subsequent interactions by homodimerization and heterodimerization, via conserved BH3 domains.…”

mentioning

confidence: 99%

Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils

Dewson

Cohen

Wardlaw

2001

Blood

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The apoptosis and subsequent clearance of eosinophils without histotoxic mediator release is thought to be crucial in the resolution of airway inflammation in asthma. Interleukin-5 (IL-5) is a potent suppressor of eosinophil apoptosis. The mechanism by which IL-5 inhibits spontaneous eosinophil apoptosis was investigated. Freshly isolated eosinophils constitutively expressed the conformationally active form of Bax in the cytosol and nucleus. During spontaneous and staurosporine-induced apoptosis, Bax underwent a caspase-independent translocation to the mitochondria, which was inhibited by IL-5. Eosinophil apoptosis was associated with the release of cytochrome c from the mitochondria, which was also inhibited by IL-5. IL-5 and the cell-permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (z-VAD.fmk), prevented phosphatidylserine (PS) externalization, although only IL-5 inhibited loss of mitochondrial membrane potential (⌬⌿m). Peripheral blood eosinophils endogenously expressed "initiator" caspase-8 and -9, and "effector" caspase-3, -6, and -7. Spontaneous eosinophil apoptosis was associated with processing of caspase-3, -6, -7, -8, and -9. IL-5 and z-VAD.fmk prevented caspase activation in spontaneous apoptosis. The results suggest that spontaneous eosinophil apoptosis involves Bax translocation to the mitochondria, cytochrome c release, caspase-independent perturbation of the mitochondrial membrane, and subsequent activation of caspases. IL-5 inhibits spontaneous eosinophil apoptosis at a site upstream of Bax translocation. IntroductionEosinophils play a pivotal role in the pathogenesis of asthma and allergic disease. 1,2 Apoptosis and efficient clearance of apoptotic cells without histotoxic mediator release is thought to be crucial in the resolution of airway inflammation, 3 and delayed eosinophil apoptosis has an association with asthma, inhalant allergy, and atopic dermatitis. 4,5 The accumulation and persistence of eosinophils at sites of inflammation are mediated at least in part by extended survival in response to circulating hematopoietins interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Eosinophils rapidly undergo apoptosis unless exposed to these cytokines in vitro 6,7 and in vivo. 8,9 The mechanism by which IL-5 prevents apoptosis in eosinophils is largely unknown.The Bcl-2 homologues are critical regulators of the apoptotic pathway, with interactions between proapoptotic (Bax, Bik, Bim, Bak) and antiapoptotic (Bcl-2, Bcl-x L ) proteins controlling the release of apoptogenic factors from mitochondria 10,11 and subsequent activation of caspases, the conserved death proteases of the cell. Previous reports investigating the role of Bcl-2 homologues in eosinophils have concentrated on the level of protein expression. Human peripheral blood eosinophils endogenously express relatively high levels of proapoptotic Bax and antiapoptotic Bcl-x L , with little or no detectable antiapoptotic Bcl-2 expression, 12,13 although there is some ...

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“…On the one hand, inflammatory cells, especially eosinophils, are known to play an important role in the onset and maintenance of asthma (Vignola et al, 1999;Druilhe et al, 2000), while the inhibition of inflammatory cell apoptosis in acute asthma is associated with the expression of pro-and antiapoptotic genes (Jang et al, 2000). bcl-2 is a type of apoptosis suppression gene, while bax or p53 are examples of proapoptotic genes.…”

Section: Discussionmentioning

confidence: 98%

“…It also could increase asthma morbidity and aggravate asthma symptoms by enhancing the sensitivity of asthma patients to antigen (Grella et al, 2002). Although the pathogenesis of asthma is still not clear, inhibition of cell apoptosis might play an important role in the development of asthma (Jang et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Effects of sulfur dioxide on expressions of p53, bax and bcl-2 in lungs of asthmatic rats

Xie¹,

Li²,

Fan³

et al. 2009

Inhalation Toxicology

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Inhibition of cell apoptosis is an increasingly important factor in modulating airway inflammation in asthma, which is related to environmental pollutants. To investigate the effects of sulfur dioxide (SO(2)) on the mRNA and protein expressions of apoptosis-related genes in lungs from asthmatic rats, male Wistar rats were challenged by ovalbumin (OVA) or SO(2) (2 ppm) inhalation alone or together. Examinations were performed 24 h after the last treatment. The mRNA and protein levels of p53, bax, and bcl-2 were analyzed in lungs using real-time reverse transcription-polymerase chain reaction (RT-PCR) assay and Western blot analysis, respectively. The results indicated that increases of bcl-2 or decreases of p53 and bax mRNA and protein levels were not significant in lungs of rats exposed to SO(2) alone, compared with controls, but elevated or reduced levels of these genes appeared in lungs of asthmatic rats exposed to SO(2) plus OVA, compared with controls, suggesting that SO(2) exposure could result in OVA-induced increases or decreases of transcription and translation levels of these apoptosis-related genes in rat lungs, and may have relations to airway inflammation in asthma. The regulation mechanism of apoptosis in asthma disease exposure to SO(2) needs further study.

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Bcl-2 expression in sputum eosinophils in patients with acute asthma

Cited by 22 publications

References 17 publications

Granulocyte apoptosis in the pathogenesis and resolution of lung disease

Granulocyte apoptosis in the pathogenesis and resolution of lung disease

Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils

Effects of sulfur dioxide on expressions of p53, bax and bcl-2 in lungs of asthmatic rats

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