PROTECTION OF HUMAN RESPIRATORY EPITHELIUM FROM PSEUDOMONAS-AERUGINOSA ADHERENCE BY PHOSPHATIDYLGLYCEROL LIPOSOMES

The ability of phosphatidylglycerol (DSPG) liposomes to prevent adhere nce of Pseudomonas aeruginosa to primary cultures of non-cystic fibros is (CF) and Delta F508 homozygous CF human respiratory epithelium was studied. The culture model was characterized by the simultaneous prese nce of various cellular phenotypes: well-differentiated respiratory ep ithelial cells, ciliated and nonciliated cells, and migrating cells wh ich can be assimilated into a regenerating epithelium after injury. DS PG liposomes significantly decreased the binding of P. aeruginosa to m igrating cells of both non-CF and Delta F508 homozygous CF cultures co mpared with control cultures (35.5 x 10(-3) +/- 8.1 x 10(-3) bacteria per mu m(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 mu m(2) ver sus 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 bo und to migrating cells in both non-CF cultures and Delta F508 homozygo us CF cultures was significantly decreased (14.4 +/- 3 bacteria per ag gregate 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 aggre gate [P < 0.01], respectively). Moreover, the control cultures were ch aracterized by a differential P. aeruginosa adherence according to bot h the cellular phenotype and the mutation. The migrating cells bound m ore bacteria than the stationary cells of both non-CF and Delta F508 h omozygous 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 mu m(2) versus 35.5 X 10(-3) +/- 8.1 X 10(-3) bacter ia per mu m(2), P < 0.001). These results suggest that DSPG liposomes are able to decrease P. aeruginosa adherence to CF and non-CF respirat ory epithelium, particularly to migrating cells, which mimic a regener ating epithelium after injury. DSPG liposomes could also represent a h ydrophobic barrier limiting the deleterious action of P. aeruginosa ex oproducts.