Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis

Watt, Alison; Brown, Vanessa; Courtney, Jo‐Maree; Kelly, Mary; Garske, Luke; Elborn, J. Stuart; Ennis, Madeleine

doi:10.1136/thx.2003.008037

Cited by 95 publications

(84 citation statements)

References 39 publications

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“…These observations are in keeping with studies showing reduced apoptosis of blood and bronchoalveolar lavage neutrophils in acute lung inflammation, such as respiratory distress syndrome, pneumonia [25,26] and exacerbations of bronchiectasis [27]. Future studies are needed to investigate the effects of COPD exacerbations on airway neutrophil survival.…”

Section: Discussionsupporting

confidence: 49%

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Rytilä

Plataki²,

Bucchieri³

et al. 2006

European Respiratory Journal

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Neutrophilic airway inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD) and correlates with disease severity. The mechanisms that determine the extent of neutrophilia could involve increased influx or prolonged survival of neutrophils. The aim of the study was to assess whether neutrophil pro-survival mechanisms are increased in the airways of subjects with COPD owing to the presence of anti-apoptotic factors in the bronchial lining fluid.Induced sputum samples were collected from 20 subjects with stable COPD, 14 healthy smokers and 14 healthy controls. Quantification of apoptotic neutrophils was based on typical morphological cell changes. Anti-apoptotic, pro-survival activity in the sputum was studied by culturing peripheral blood neutrophils with the fluid phase of induced sputum. Apoptosis was assessed both by morphology and flow cytometry using Annexin V/7-aminoactinomycin D staining.COPD patients and healthy smokers had significantly higher percentages of sputum neutrophils than healthy controls. However, there were no significant differences between the three subject groups in either the proportion of apoptotic neutrophils in sputum or the in vitro antiapoptotic activity detected in the sputum fluid phase.In conclusion, prolonged survival of neutrophils in sputum is not a feature of chronic obstructive pulmonary disease and cannot explain the increased numbers of airway neutrophils in this disease.

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Section: Discussionsupporting

confidence: 49%

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Rytilä

Plataki²,

Bucchieri³

et al. 2006

European Respiratory Journal

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“…Airway epithelial cells are increasingly recognised to operate as ''effector'' cells that produce a wide range of inflammatory cytokines and growth factors [23]. The cytokines IL-8, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important in neutrophil activation, recruitment and longevity [24]. We therefore investigated the effects of IL-17 on the production of these mediators by ex vivo cultures of PBECs from people with CF.…”

Section: Resultsmentioning

confidence: 99%

Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease

Brodlie¹,

McKean²,

Johnson³

et al. 2010

European Respiratory Journal

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Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells.Immunohistochemistry was performed on explanted CF lungs and compared with the nonsuppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs.Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p50.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells?mm -1 compared with 9 cells?mm -1 basement membrane, p50.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor.In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.

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“…Cell suspensions were then labeled with annexin V-FITC (AV) and propidium iodide (PI) (Pharmingen). Flow cytometry was performed as previously described (31). Full experimental details are provided in the online supplement.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

Simvastatin Decreases Lipopolysaccharide-induced Pulmonary Inflammation in Healthy Volunteers

Shyamsundar¹,

McKeown²,

O'Kane³

et al. 2009

Am J Respir Crit Care Med

221

182

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Rationale: Simvastatin inhibits inflammatory responses in vitro and in murine models of lung inflammation in vivo. As simvastatin modulates a number of the underlying processes described in acute lung injury (ALI), it may be a potential therapeutic option. Objectives: To investigate in vivo if simvastatin modulates mechanisms important in the development of ALI in a model of acute lung inflammation induced by inhalation of lipopolysaccharide (LPS) in healthy human volunteers. Methods: Thirty healthy subjects were enrolled in a double-blind, placebo-controlled study. Subjects were randomized to receive 40 mg or 80 mg of simvastatin or placebo (n 5 10/group) for 4 days before inhalation of 50 mg LPS. Measurements were performed in bronchoalveolar lavage fluid (BALF) obtained at 6 hours and plasma obtained at 24 hours after LPS challenge. Nuclear translocation of nuclear factor-kB (NF-kB) was measured in monocyte-derived macrophages. Measurements and Main Results: Pretreatment with simvastatin reduced LPS-induced BALF neutrophilia, myeloperoxidase, tumor necrosis factor-a, matrix metalloproteinases 7, 8, and 9, and C-reactive protein (CRP) as well as plasma CRP (all P , 0.05 vs. placebo). There was no significant difference between simvastatin 40 mg and 80 mg. BALF from subjects post-LPS inhalation induced a threefold up-regulation in nuclear NF-kB in monocyte-derived macrophages (P , 0.001); pretreatment with simvastatin reduced this by 35% (P , 0.001). Conclusions: Simvastatin has antiinflammatory effects in the pulmonary and systemic compartment in humans exposed to inhaled LPS. Clinical trial registered with www.controlled-trials.com (ISRCTN21056528).

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Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis

Abstract: This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.

Cited by 95 publications

References 39 publications

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease

Simvastatin Decreases Lipopolysaccharide-induced Pulmonary Inflammation in Healthy Volunteers

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