Analysis of factors that characterize health impairment in patients with chronic respiratory failure

M. Carone, G. Bertolotti, F. Anchisi, A. M. Zotti, C. F. Donner, P. W. Jones, On Behalf of the Quality of Life in Chronic Respiratory Failure Group
1999 European Respiratory Journal  
Fibronectin and a5b1 integrin mediate binding of Pseudomonas aeruginosa to repairing airway epithelium. ABSTRACT: Initial infection of the airway by Pseudomonas aeruginosa may occur through a variety of bacterial strategies including binding to epithelial receptors present at the surface of the respiratory epithelium. In order to characterize the adherence sites for P. aeruginosa in damaged and repairing bronchial tissue, an ex vivo model of airway epithelial injury and repair was developed
more » ... r was developed using primary cell cultures of nasal cells from 14 subjects with polyposis. P. aeruginosa strongly adhered to flattened dedifferentiated (FD) bronchial and nasal cytokeratin 13-positive epithelial cells in the process of migration for repair. In in vitro experiments, competitive binding inhibition assays demonstrated that a5b1 integrins and cellular fibronectin, in particular the RGD sequence, are receptors involved in P. aeruginosa adherence to FD nasal epithelial cells. Fluorescent cell sorting analysis and immunofluorescence techniques revealed that the a5b1 integrins are overexpressed and apically exposed in FD nasal epithelial cells. One 50 kDa outer membrane protein was identified in piliated and nonpiliated strains of P. aeruginosa that was involved in binding to cellular fibronectin and a5b1 epithelial integrins. These results demonstrate that Pseudomonas aeruginosa adherence is related to the dedifferentiation of airway epithelium during the repair process which unmasks and upregulates the a5b1 integrin expression and induces active synthesis of cellular fibronectin. These epithelial receptors are then used by a Pseudomonas aeruginosa 50 kDa outer membrane protein as sites of bacterial adherence. Eur Respir J 1999; 13: 1301±1309.
doi:10.1183/09031936.99.13613019 pmid:10445604 fatcat:6xzfzint6zc7lj3awbq2sjsluq