Protection of human respiratory epithelium from Pseudomonas aeruginosa adherence by phosphatidylglycerol liposomes

Abstract

The ability of phosphatidylglycerol (DSPG) liposomes to prevent adherence of Pseudomonas aeruginosa to primary cultures of non-cystic fibrosis (CF) and delta F508 homozygous CF human respiratory epithelium was studied. The culture model was characterized by the simultaneous presence of various cellular phenotypes: well-differentiated respiratory epithelial cells, ciliated and nonciliated cells, and migrating cells which can be assimilated into a regenerating epithelium after injury. DSPG liposomes significantly decreased the binding of P. aeruginosa to migrating cells of both non-CF and delta F508 homozygous CF cultures compared with control cultures (35.5 x 10(-3) +/- 8.1 x 10(-3) bacteria per micron 2 versus 23.9 x 10(-3) +/- 2.5 x 10(-3); P < 0.01 for non-CF cultures and 88.8 x 10(-3) +/- 17.2 x 10(-3) bacteria per micron 2 versus 29.1 x 10(-3) +/- 0.6 x 10(-3), P < 0.001 for CF cultures). After treatment with DSPG liposomes, the size of P. aeruginosa aggregates bound to migrating cells in both non-CF cultures and delta F508 homozygous CF cultures was significantly decreased (14.4 +/- 3 bacteria per aggregate versus 11.9 +/- 2.5 bacteria per aggregate [P < 0.05] and 29.9 +/- 8.4 bacteria per aggregate versus 17.3 +/- 2.3 bacteria per aggregate [P < 0.01], respectively). Moreover, the control cultures were characterized by a differential P. aeruginosa adherence according to both the cellular phenotype and the mutation. The migrating cells bound more bacteria than the stationary cells of both non-CF and delta F508 homozygous CF cultures. The CF migrating cells bound significantly more bacteria than the non-CF migrating cells (88.8 x 10(-3) +/- 17.2 x 10(-3) bacteria per microns 2 versus 35.5 x 10(-3) +/- 8.1 x 10(-3) bacteria per micron 2, P < 0.001). These results suggest that DSPG liposomes are able to decrease P. aeruginosa adherence to CF and non-CF respiratory epithelium, particularly to migrating cells, which mimic a regenerating epithelium after injury. DSPG liposomes could also represent a hydrophobic barrier limiting the deleterious action of P. aeruginosa exoproducts.