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Lactoferrin is an important antimicrobial protein in the airways. In this study lactoferrin activity and Pseudomonas biofilm formation were investigated in sputum and bronchoalveolar lavage (BAL) fluid from age and genotype matched cystic fibrosis (CF) patients with and without P aeruginosa colonisation (n = 20).
In P aeruginosa positive subjects the sputum lactoferrin concentration, corrected for sputum neutrophils, was significantly lower (p<0.003) and cathepsin activity significantly increased (p<0.012). Degradation of lactoferrin was observed in the presence of BAL fluid from these patients and prevented using specific cathepsin inhibitors. Lactoferrin, once cleaved by cathepsin (B, L or S), showed significantly reduced activity against P aeruginosa (p = 0.033). In addition, lactoferrin was found significantly to inhibit Pseudomonas biofilm formation (p<0.001), but not after cleavage with cathepsins. In keeping with these findings, sputum from the P aeruginosa positive subjects had significantly reduced ability to inhibit biofilm formation compared with non-P aeruginosa sputum samples (p<0.01).
This study shows that increased cathepsin activity in CF patients with sputum P aeruginosa results in degradation of lactoferrin. The consequence is a loss of antimicrobial activity against P aeruginosa and of the host ability to prevent biofilm formation. This mechanism may have an important role in the development of colonisation with P aeruginosa in CF with resulting clinical deterioration.