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S46 Neutrophil vascular endothelial growth factor (VEGF) as a driving force for angiogenesis in bronchiectasis?
  1. CC Cole1,
  2. SC Carnell2,
  3. KJ Jiwa3,
  4. JB Birch4,
  5. KH Hester1,
  6. CW Ward1,
  7. JS Simpson1,
  8. ADS De Soyza2
  1. 1Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
  2. 2Newcastle Clinical Trials Unit, Newcastle Upon Tyne, UK
  3. 3Sir William Leech Centre for Lung Research, Freeman Hospital, Newcastle Upon Tyne, UK
  4. 4Institute for Cell and Molecular Biosciences, Newcastle Upon Tyne, UK

Abstract

Introduction Bronchiectasis (BR) in a pulmonary disease thought to involve a characteristic dilation of the bronchi resulting from a cycle of airway infection and inflammation. This inflammation is believed to be driven by neutrophils, which are present in the BR lung in high number. Vascular endothelial growth factor (VEGF) is a pro-angiogenic cytokine that may be upregulated in BR and could contribute towards creating a pro-angiogenic airway environment by supporting neutrophil migration into the airway tissue, however this has yet to be shown.

Aims 1) Examine the BR airway for any indications of increased angiogenesis, 2) Assess the ability of neutrophils to secrete VEGF upon stimulation in vitro, 3) Evaluate sera/sputa samples VEGF concentration to determine if VEGF could act as a biomarker for BR severity.

Methods Healthy volunteer (HV) and BR endobronchial biopsies were stained with a HRP conjugated anti-CD31 antibody, allowing blood vessels to be counted in a blinded manner. Peripheral blood neutrophils isolated from HV were stimulated (e.g. with TNF-α or bacterial PAMPs) for 4 hours, VEGF levels in supernatants were then quantified using ELISA. A VEGF ELISA was also used to determine VEGF concentration in sera and sputa samples from BR patients (n = 115), categorised by bronchiectasis severity index (BSI) scores and sera samples from HV controls (n = 26)

Results Endobronchial biopsies from BR airways had a significantly (p < 0.05) higher number of blood vessels per mm of basement membrane than HV samples (18 and 9 blood vessels/mm basement membrane respectively). Stimulation of HV neutrophils with a variety of molecules (PMA, fMLP, LPS, TNF-α etc.) resulted in a significant increase in VEGF secretion compared to unstimulated (p < 0.05). Although elevated VEGF was found in some patient samples there was no significant correlation between sera/sputa VEGF and individual patient BSI scores.

Conclusion The increased presence of vascular tissue seen in BR could indicate a pro-angiogenic airway environment in BR. The in vitro data collected also show that a variety of stimulants can initiate secretion of VEGF by neutrophils. However, our data does not suggest that VEGF levels in sera or sputa can be used to predict disease severity.

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