Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml-1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

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The ability of phosphatidylglycerol (DSPG) liposomes to prevent adherence of Pseudomonas aeruginosa to primary cultures of non-cystic fibrosis (CF) and AF508 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 AF508 homozygous CF cultures compared with control cultures (35.5 x 10-3 ± 8.1 X 10-3 bacteria per tLm2 versus 23.9 x 10-3 ± 2.5 X 10-3; P < 0.01 for non-CF cultures and 88.8 X 10-± 17.2 X i03 bacteria per jim2 versus 29.1 X ±0-± 0.6 X 10-, 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 AF508 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 < 0.011, 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 AF508 homozygous CF cultures. The CF migrating cells bound significantly more bacteria than the non-CF migrating cells (88.8 x i0-3 ± 17.2 X i03 bacteria per jim2 versus 35.5 X i0-3 ± 8.1 X i0-3 bacteria per jim2, 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.