Abstract

Introduction: Heparin Binding Protein (HBP) is a cationic antimicrobial protein synthesised in neutrophils, and recently implicated as a sputum marker of airway inflammation and bacterial load in patients with cystic fibrosis. A label free proteomic study of bronchiectasis sputum identified HBP as a potential marker of disease severity.

Aim: Determine if HBP is related to bronchiectasis severity and its effect on respiratory epithelial cell function.

Methods: HBP was measured in soluble sputum by ELISA. Severity of bronchiectasis was evaluated using the BSI and lung function by FEV1. Ciliated epithelial cells were grown at air liquid interface (n=5). HBP was added apically at 385ug/ml and ciliary beat frequency and transepithelial resistance (TEER) were measured.

Results: 60 bronchiectasis patients were included. Mean HBP concentration was 40.6ug/ml (range 0-596ug/ml). HBP correlated with severity of disease. FEV1 % predicted (r= -0.52, p=0.0015) and was higher in patients with Pseudomonas aeruginosa infection (p=0.0001).

Addition of HBP to respiratory epithelial cells revealed a mean (stdev) -20%(7%) reduction in ciliary beat frequency which could be recovered by washing (p<0.01). HBP compromised epithelial integrity. TEER rapidly reduced -26% (15%) following addition of HBP compared to buffer alone 11%(11%) p=0.04.

Conclusion: There is a strong correlation between sputum HBP concentration and bronchiectasis disease severity. The effect of HBP on ciliary beat frequency and epithelial integrity at concentrations found in sputum suggest a potential impact on epithelial defence against respiratory infection.