Fibronectin and alpha 5 beta 1 integrin mediate binding of Pseudomonas aeruginosa to repairing airway epithelium

Initial infection of the airway by Pseudomonas aeruginosa may occur through a variety of bacterial strategies including binding to epithelial receptor s present at the surface of the respiratory epithelium, In order to characterize the adherence sites for P. aeruginosa in damaged a nd repairing bronchial tissue, an ex vivo model of airway epithelial injury and repair was developed using primary cell cultures of nasal cells from 1 4 subjects with polyposis. P. aeruginosa strongly adhered to flattened dedifferentiated (FD) bronchial and nasal cytokeratin 13-positive epithelial cells in the process of migra tion for repair, In in vitro experiments, competitive binding inhibition as says demonstrated that alpha 5 beta 1 integrins and cellular fibronectin, i n particular the RGD sequence, are receptors involved in P. aeruginosa adhe rence to FD nasal epithelial cells, Fluorescent cell sorting analysis and i mmunofluorescence techniques revealed that the alpha 5 beta 1 integrins are overexpressed and apically exposed in FD nasal epithelial cells. One 50 kD a outer membrane protein was identified in piliated and nonpiliated strains of P. aeruginosa that was involved in binding to cellular fibronectin and alpha 5 beta 1 epithelial integrins. These results demonstrate that Pseudomonas aeruginosa adherence is related to the dedifferentiation of airway epithelium during the repair process whi ch unmasks and upregulates the alpha 5 beta 1 integrin expression and induc es active synthesis of cellular fibronectin, These epithelial receptors are then used by a Pseudomonas aeruginosa 50 kDa outer membrane protein as sit es of bacterial adherence.