Airway neutrophilian in bronchiectasis: the role of TNF-α in vivo

Session - Respiratory & Critical Care Medicine: no. S-RC-5published_or_final_versio

Up-regulation of circulating adhesion molecules in stable bronchiectasis

Session - Respiratory & Critical Care Medicine: no. S-RC-4published_or_final_versio

Downregulation of endothelin (ET)-1 and interleukin (IL)-8 expression in human respiratory mucosa by Pseudomonas aeruginosa pyocyanin (pyo) and 1-hydroxy-phenazine (HP)

published_or_final_versio

Down-expression of inducible nitric oxide synthase (iNOS) and endothelial (Enos) proteins and mRNA iNOS in bronchiectasis in vivo

published_or_final_versio

The effects of gender on exhaled Nitric Oxide (NO) production among volunteers

published_or_final_versio

Delayed woundhealing after tooth extraction and self–reportedkyphosis in Japanese men and women

It is unclear whether osteoporosis itself is a main risk factor for delayed wound healing after tooth extraction in humans. In this study, we evaluated the association between experience of delayed wound healing after last tooth extraction and self-reported kyphosis, with the possibility of having vertebral fractures, in Japanese patients. Among the 1,504 patients who responded to the structured questionnaire survey, 518 patients (134 men and 384 women) aged 55-97 years finally participated in this study. Patients who self-reported mild-moderate kyphosis were more likely to have problematic delayed wound healing after last tooth extraction than those who reported severe kyphosis (odds ratio [OR] 4.98; 95% confidence interval [CI], 1.86-13.38 and OR 2.30; 95% CI, 0.52-10.22, respectively) (p for trend = 0.005). Japanese patients with vertebral fractures may have a higher risk of having problematic delayed wound healing after tooth extraction

Pseudomonas aeruginosa adherence to human basement membrane collagen in vitro

The mechanisms for Pseudomonas aeruginosa colonisation in the airways of patients with bronchiectasis and cystic fibrosis are poorly understood. P. aeruginosa could evade mucociliary clearance by adhering to the basement membrane at areas denuded of,intact respiratory epithelium. The authors have developed an in vitro model to study P. aeruginosa adherence to human basement membrane type-IV collagen by using scanning electron microscopy. P. aeruginosa adherence density was determined as the number of P. aeruginosa per 20 microscope fields (2,000x) to log inocular size after incubation at 37°C for 45 min. The presence of phytohaemagglutinin (PHA)-E, which binds specifically to D-galactose-β1-4-D-N-acetylglucosamine, significantly reduced P. aeruginosa adherence density compared with control. The presence of heparin and calcium also significantly reduced P. aeruginosa adherence density. P. aeruginosa adherence was not affected by the presence of proline, trans-hydroxyproline, glycine, galactose, N-acetylneuraminic acid, N-acetylglucosamine or Arachis hypogea. Pseudomonas aeruginosa adherence probably acts via recognition of the D-galactose-β1-4-D-N-acetylglucosamine sequence on type-IV collagen and this process could be inhibited by heparin and calcium. As persistent Pseudomonas aeruginosa colonisation is detrimental to patients with cystic fibrosis and bronchiectasis and there is currently no effective treatment for its eradication, these results could lead to novel therapy for persistent Pseudomonas aeruginosa infection.link_to_OA_fulltex

Up-regulation of circulating adhesion molecules in bronchiectasis

Adhesion molecules are expressed on the surface of endothelial cells and leukocytes and are responsible for mediating the migration of intravascular leukocytes into inflamed tissue. Intensive recruitment of neutrophils into the airways occurs in bronchiectasis, although little is known about the role of adhesion molecules in this process. The authors, therefore, determined serum levels of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in stable bronchiectasis patients (n=37) and healthy control subjects (n=17), and evaluated their relationship with clinical markers of disease severity in bronchiectasis. Serum levels of E-selectin, ICAM-1 and VCAM-1 in bronchiectasis patients were significantly higher than those in control subjects (p=0.02, <0.0001 and 0.0002 respectively). Both E-selectin and ICAM-1 levels were inversely related to forced expiratory volume in one second (FEV1)% predicted (r=-0.57, p<0.001; and r=-0.53, p=0.001 respectively), and FVC% predicted (r=-0.52, p=0.002; and r=-0.46, p=0.005). This was not the case for VCAM-1 levels. There was a correlation between serum ICAM-1 levels and 24 h sputum volume (r=-0.34, p= 0.04). Serum E-selectin and ICAM-1, but not VCAM-1, levels showed correlation with the number of lung lobes affected by bronchiectasis (r=0.35, p=0.04 and r=0.34, p=0.04 respectively). These original observations strongly suggest that E-selectin, intercellular adhesion molecule-1 and Vascular adhesion molecule-1 could play a significant role in the pathogenesis of bronchiectasis. (C) ERS Journals Ltd 2000.link_to_OA_fulltex

Overexpression of matrix metalloproteinase-8 and -9 in bronchiectatic airways in vivo

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process. Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP-8 and MMP-9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP-8, MMP-9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell·mm -2 of the lamina propria by using an image analysis system. There were significantly higher densities of MMP-8 and MMP-9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP-8 and MMP-9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP-8 with neutrophil and MMP-9 with macrophage densities. An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.link_to_OA_fulltex