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J Cyst Fibros. 2017 Jan;16(1):49-57. doi: 10.1016/j.jcf.2016.10.006. Epub 2016 Nov 10.

Bacterial proteases and haemostasis dysregulation in the CF lung.

Author information

1
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
2
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; Department of Physiology, Development and Neuroscience, Selwyn College, University of Cambridge, CB2 3DY, United Kingdom.
3
Centre for Infection and Immunity, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, C-TRIC Building, Altnagelvin Area Hospital, University of Ulster, Londonderry, BT47 6SB, United Kingdom.
4
Centre for Infection and Immunity, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
5
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom. Electronic address: l.martin@qub.ac.uk.

Abstract

BACKGROUND:

Pathogenic bacteria which chronically colonise the cystic fibrosis (CF) lung produce a number of virulence determinants, including distinct proteolytic activities. The potential role bacterial proteases play on haemostatic dysregulation within the CF lung is, however, poorly defined, despite haemoptysis being a common complication in CF.

METHODS:

The potential impact of known CF pathogens (Pseudomonas aeruginosa and Burkholderia cepacia complex spp.) on haemostasis was examined for their ability to degrade fibrinogen and dysregulate fibrin clot formation and platelet aggregation.

RESULTS:

Results demonstrate that key CF pathogens growing as a biofilm on mucin exhibit considerable fibrinogenolytic activity, resulting in fibrinogen breakdown, impaired clot formation, and modulation of platelet aggregation. Human neutrophil elastase may also contribute to fibrinogen breakdown and dysregulated clot formation at high concentration.

CONCLUSION:

Bacterial-derived proteases may play an important role in the dysregulation of airway haemostasis, and potentially contribute to episodes of haemoptysis within the CF lung.

KEYWORDS:

Burkholderia cenocepacia; Burkholderia multivorans; Coagulation; Cystic fibrosis; Haemoptysis; Haemostasis; Platelet aggregation; Pseudomonas aeruginosa

PMID:
27839953
DOI:
10.1016/j.jcf.2016.10.006
[Indexed for MEDLINE]
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