Cigarette Smoke Prevents Apoptosis through Inhibition of Caspase Activation and Induces Necrosis

Wickenden, Julie A; Clarke, Murray C.H.; Rossi, Adriano G.; Rahman, Irfan; Faux, Stephen P.; Donaldson, Kenneth; MacNee, William

doi:10.1165/rcmb.2002-0235oc

Cited by 113 publications

(92 citation statements)

References 52 publications

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“…Although this finding supports the notion that necrosis rather than apoptosis is the usual death mode of structural cells [15], it must not be forgotten that apoptosis of structural cells occurs more frequently in more chronic situations. The study also found numerous apoptotic neutrophils and neutrophils in the process of secondary necrosis, suggesting that the apoptotic process is not too swift to be detected.…”

Section: Discussionsupporting

confidence: 70%

Direct evidence of secondary necrosis of neutrophils during intense lung inflammation

Rydell‐Törmänen¹

2006

Eur Respir J

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Several pulmonary inflammatory conditions are characterised by infiltration of neutrophils. Normally, neutrophils are silently removed by apoptosis, followed by phagocytosis. However, if phagocytosis fails, apoptotic cells undergo secondary necrosis. Recent findings of increased levels of the pan-necrosis marker lactate dehydrogenase in bronchoalveolar lavage from lipopolysaccharide-exposed mice implies potential involvement of secondary necrosis. Using a similar model, this study aimed to identify the source of lactate dehydrogenase and to search for direct histological evidence of secondary necrosis.Lipopolysaccharide (LPS) was administered to the lungs of BALB/c mice, and bronchoalveolar lavage and tissue samples were collected 4, 12, 24, 36, 48, 60 and 72 h after administration. LPS induced a patchy neutrophil-rich lung inflammation, where the numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling-positive neutrophils were increased at 12 h and onwards. Lavage levels of neutrophils and lactate dehydrogenase increased significantly at 4 and 24 h, respectively. Detailed electron microscopic assessment of neutrophil activation and death modes revealed that up to 14% of the neutrophils were undergoing secondary necrosis, whereas apoptotic or primary necrotic structural cells were rarely found.In summary, this study provides direct evidence that secondary necrosis of neutrophils is a common process during intense lung inflammation. This implies that neutrophil apoptosis may cause rather than resolve airway inflammation.

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Section: Discussionsupporting

confidence: 70%

Direct evidence of secondary necrosis of neutrophils during intense lung inflammation

Rydell‐Törmänen¹

2006

Eur Respir J

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“…We found in this study that ECS exposure of larval ‰ies decreased the level of total glutathione (that is, GSH plus GSSG) in the bodies of all four strains examined. According to Wickenden and colleagues, who observed in cultured human cells that the total glutathione decreased following treatment with cigarette smoke condensate, GSH may conjugate with cigarette smoke components, as GSH is utilized in living cells in detoxiˆcation processes by forming conjugates with xenobiotics (31). This interpretation could also be applied to the present data.…”

Section: Discussionsupporting

confidence: 61%

Exposure to Cigarette Smoke Increases Urate Level and Decreases Glutathione Level in Larval Drosophila melanogaster

Fujiwara

Hamatake

Arimoto

et al. 2011

Genes and Environment

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Recently, we reported experimental evidence to support the notion that in Drosophila melanogaster, urate is involved in defense against toxic eŠects of environmental cigarette smoke (ECS). To obtain further information pertaining to the defense mechanisms involving urate and other antioxidants, the present study measured the levels of urate, its precursors and glutathione, and SOD activity in larval ‰ies of wild-type strains (Oregon-R and Canton-S) and two urate-null mutant strains (ma-l and ry 1 ) following exposure to ECS for various durations. In both wild type strains, unlike the case in either of the mutant strains, the urate level signiˆcantly increased above the basal level in a manner dependent on the duration of ECS exposure. Similar increases in the level of urate precursors were found in Canton-S and in both of the urate-null strains. There was a slight increase in glutathione level above the control level following ECS exposure for a short time, followed by an exposure-dependent decrease to less than 60% of the control level within the exposure range used in all of the four strains. On the other hand, no appreciable change was found in the SOD activity prior to or following ECS exposure, irrespective of the strain examined. In terms of the survival of treated larvae to adulthood under the conditions used for the measurements of urate and others, it was found that wild-type strain Canton-S was as sensitive as the urate-null mutant strains and clearly more sensitive than wild-type strains Oregon-R and Hikone-R. This was so despite the fact that, compared with Oregon-R, Canton-S contained urate at relatively higher levels prior to and following ECS exposure, and that the glutathione levels in Canton-S prior to and following treatment were comparable with those in other strains. These results are discussed with respect to the involvement of urate and glutathione in defense against the toxicity of ECS and the possible existence of another defense mechanism which is deˆcient in the Canton-S strain.

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“…These cells secrete inflammatory cytokines, proteases, and reactive oxygen species, causing necrosis, tissue damage, and further amplification of the inflammatory response with enhanced recruitment of neutrophils into the lung. Tissue damage promotes the release of inflammatory mediators and inhibits lung tissue repair functions, further increasing the tissue damage in the lungs of smokers (35,38,39). It is generally accepted, although it has not been formally proven, that these alterations could allow access of microorganisms to the otherwise sterile lungs, thereby leading to microbial colonization (28)(29)(30).…”

mentioning

confidence: 99%

Nontypeable Haemophilus influenzae Clearance by Alveolar Macrophages Is Impaired by Exposure to Cigarette Smoke

et al. 2009

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Nontypeable Haemophilus influenzae (NTHI) is an opportunistic gram-negative pathogen that causes respiratory infections and is associated with progression of respiratory diseases. Cigarette smoke is a main risk factor for development of respiratory infections and chronic respiratory diseases. Glucocorticoids, which are anti-inflammatory drugs, are still the most common therapy for these diseases. Alveolar macrophages are professional phagocytes that reside in the lung and are responsible for clearing infections by the action of their phagolysosomal machinery and promotion of local inflammation. In this study, we dissected the interaction between NTHI and alveolar macrophages and the effect of cigarette smoke on this interaction. We showed that alveolar macrophages clear NTHI infections by adhesion, phagocytosis, and phagolysosomal processing of the pathogen. Bacterial uptake requires host actin polymerization, the integrity of plasma membrane lipid rafts, and activation of the phosphatidylinositol 3-kinase (PI3K) signaling cascade. Parallel to bacterial clearance, macrophages secrete tumor necrosis factor alpha (TNF-␣) upon NTHI infection. In contrast, exposure to cigarette smoke extract (CSE) impaired alveolar macrophage phagocytosis, although NTHI-induced TNF-␣ secretion was not abrogated. Mechanistically, our data showed that CSE reduced PI3K signaling activation triggered by NTHI. Treatment of CSE-exposed cells with the glucocorticoid dexamethasone reduced the amount of TNF-␣ secreted upon NTHI infection but did not compensate for CSE-dependent phagocytic impairment. The deleterious effect of cigarette smoke was observed in macrophage cell lines and in human alveolar macrophages obtained from smokers and from patients with chronic obstructive pulmonary disease.

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Cigarette Smoke Prevents Apoptosis through Inhibition of Caspase Activation and Induces Necrosis

Cited by 113 publications

References 52 publications

Direct evidence of secondary necrosis of neutrophils during intense lung inflammation

Direct evidence of secondary necrosis of neutrophils during intense lung inflammation

Exposure to Cigarette Smoke Increases Urate Level and Decreases Glutathione Level in Larval Drosophila melanogaster

Nontypeable Haemophilus influenzae Clearance by Alveolar Macrophages Is Impaired by Exposure to Cigarette Smoke

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