Granulocyte apoptosis in the pathogenesis and resolution of lung disease

Bianchi, Stephen; Dockrell, David H.; Renshaw, Stephen A.; Sabroe, Ian; Whyte, Moira K. B.

doi:10.1042/cs20050178

Cited by 57 publications

(47 citation statements)

References 164 publications

(157 reference statements)

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“…Our observation suggests occurrence of non-caspasedependent induction of apoptosis, which would be in agreement with the observed intermediate level of BAL PMNs in R-roscovitine + zVAD-fmk cotreatment. Few annexin V + 7-AAD + cells were measured, which could be because of either the experimental procedures or the phagocytosis (for example, by macrophages), since extracellular membrane PS targets cells for phagocytosis (13). To expand our data on R-roscovitine effects on LTA-induced pulmonary inflammation, we determined the impact of R-roscovitine on a progressing inflammatory response in the lung elicited by the clinically relevant gram-positive pathogen S. pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

“…PMNs contain and generate toxic substances that are harmful to the lung when they exocytose their granules and/or undergo uncontrolled necrosis. Therefore, successful resolution of infection entails removal of excess cellular infiltrate (11,13). Herein, apoptosis is a strong regulatory mechanism during lung inflammation (14): phagocytosis of apoptotic PMNs by macrophages reprograms macrophages to release antiinflammatory mediators, thus aiding resolution of (harmful) inflammation (15,16).…”

Section: Introductionmentioning

confidence: 99%

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R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae

Hoogendijk

Roelofs

Duitman

et al. 2012

Mol Med

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Bacterial pneumonia remains associated with high morbidity and mortality. The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Lipoteichoic acid (LTA) is an important proinflammatory component of the gram-positive bacterial cell wall. R-roscovitine, a purine analog, is a potent cyclin-dependent kinase (CDK)-1, -2, -5 and -7 inhibitor that has the ability to inhibit the cell cycle and to induce polymorphonuclear cell (PMN) apoptosis. We sought to investigate the effect of R-roscovitine on LTA-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LTA or viable S. pneumoniae in vivo. In vitro R-roscovitine enhanced apoptosis in PMNs and reduced tumor necrosis factor (TNF)-α and keratinocyte chemoattractant (KC) production in MH-S (alveolar macrophage) and MLE-12/ MLE-15 (respiratory epithelial) cell lines. In vivo R-roscovitine treatment reduced PMN numbers in bronchoalveolar lavage fluid during LTA-induced lung inflammation; this effect was reversed by inhibiting apoptosis. Postponed treatment with R-roscovitine (24 and 72 h) diminished PMN numbers in lung tissue during gram-positive pneumonia; this step was associated with a transient increase in pulmonary bacterial loads. R-roscovitine inhibits proinflammatory responses induced by the gram-positive stimuli LTA and S. pneumoniae. R-roscovitine reduces PMN numbers in lungs upon LTA administration by enhancing apoptosis. The reduction in PMN numbers caused by R-roscovitine during S. pneumoniae pneumonia may hamper antibacterial defense.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae

Hoogendijk

Roelofs

Duitman

et al. 2012

Mol Med

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“…Caspase-3 (Cas3) is the critical executioner of apoptosis, and granulocytes are susceptible to apoptosis. 37 Hypermorphic expression of…”

Section: Resultsmentioning

confidence: 99%

SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF-α signaling

2013

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Tumor-necrosis factor-a (TNF-a)-driven nuclear factor-kB (NF-kB) activation and apoptosis are opposing pathways; the growing recognition of these conflicting roles of TNF-a is perplexing. Here, we show that inflammation and apoptosis are time-phased events following TNF-a signaling and that emergence of suppressor of cytokine signaling 3 (SOCS3) expression limits the ongoing NF-kB activation and promotes apoptosis; further, we suggest an altered view of how inflammatory diseases are initiated and sustained. In vitro, TNF-a (50 ng/ml) induced granulocyte SOCS3 protein, inhibited nuclear accumulation of the p65NF-kB subunit and enhanced apoptosis, as shown by DNA laddering, annexin V positivity, and overexpression of caspase-3 and Bax in the late phase, whereas the early phase was marked by NF-kB activation. Conversely, SOCS3 knockdown by small interfering RNA (siRNA) inhibited granulocyte apoptosis and enhanced nuclear accumulation of p65 and 59 lipooxygenase expression in the late phase of TNF-a signaling. As apoptosis is associated with SOCS3 abundance, we suggest that these divergent TNF-a-driven events are time-phased, interconnected, opposing control mechanisms and one of the central features through which the immune system resolves pulmonary inflammation. Dysregulation may initiate mucosal inflammation, thus changing the landscape of asthma therapy.

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“…[3,5] Apoptosis is characterized by specific morphological and biochemical changes such as cell shrinkage, nuclear coalescence, chromatin condensation and endonuclease-catalyzed DNA breakdown followed by fragmentation of the cell into apoptotic bodies, which are phagocytozed intact without further induction of inflammation. [6,7] Apoptosis and its induction is regarded as an important mechanism in the resolution of eosinophilic inflammation [3,5,6] and it has been shown that eosinophil apoptosis is delayed in patients with asthma, inhalant allergy and atopic dermatitis [8,9]. In vitro, eosinophil apoptosis is inhibited by cytokines such as interleukin (IL) -3, IL-5 and granulocyte/macrophage colony-stimulating factor.…”

Section: Introductionmentioning

confidence: 99%

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

Hasala¹,

Giembycz²,

Janka-Junttila³

et al. 2008

Pulmonary Pharmacology & Therapeutics

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A c c e p t e d m a n u s c r i p tCaspase activities were assessed by using commercial Caspase-Glo ® 3/7, 8, and 9 luminescence assays.Histamine (10-100 µM) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells.This effect was not mediated through any of the known histamine receptors or through nonspecific activation of 5-hydroxytryptamine receptors or α-adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general.In conclusion, the data presented herein indicate that histamine induces human eosinophil apoptosis in the presence of a survival-prolonging cytokine by a mechanism that does not apparently involve the activation of any of the currently known histamine receptor subtypes.The possibility exists that another, as yet unidentified, histamine receptor may exist in human eosinophils that regulates survival, although the participation of histamine receptorindependent mechanisms cannot be excluded. 3A c c e p t e d m a n u s c r i p t

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Granulocyte apoptosis in the pathogenesis and resolution of lung disease

Cited by 57 publications

References 164 publications

R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae

R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae

SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF-α signaling

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

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