Type

Journal Article

Authors

Noel G McElvaney
Catherine M Greene
Sanjay H Chotirmall
Sonya Cosgrove

Subjects

Microbiology

Topics
physiology hemoglobins pseudomonas aeruginosa enzymology myeloblastin peptide hydrolases interleukin 10 meprin a epithelial cells leukocyte elastase serine endopeptidases microbiology cytology pseudomonas infections pneumonia bacterial toll like receptors heme cell line humans metabolism bronchoalveolar lavage fluid respiratory mucosa cystic fibrosis immunology microbial serine proteinases signal transduction genetics pathology interleukin 8 receptor epidermal growth factor metalloendopeptidases

Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway. (2010)

Abstract A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Catherine M Greene, Sanjay H Chotirmall, Sonya Cosgrove

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
3
Sanjay H Chotirmall
Royal College of Surgeons in Ireland
Total Publications: 22