Improvement of cystic fibrosis airway mucus transportability by recombinant human DNase is related to changes in phospholipid profile.
The aim of this study was to test whether changes in mucus surface properties by rhDNase treatment could be related to an increased recovery of phospholipids. Purulent sputa from 18 patients with cystic fibrosis (CF) were incubated with either rhDNase (4 microg/ml) or control excipient. The incubation of mucus samples with rhDNase induced a significant increase (p < 0.002) in the sol phase proportion (33.7 +/- 24.0%) compared with that obtained with excipient (12.6 +/- 12.4%). Phospholipids were recovered in significantly (p < 0.05) greater amounts from both mucus gel and sol phases after incubation with rhDNase. The phosphatidylglycerol content of mucus sol phase was significantly increased by rhDNase (p < 0.03), as well as the mucus gel phase surface properties and transport by ciliary activity and by cough (p < 0.05). The improvement of mucus gel surface properties and transport capacity by ciliary activity were significantly related to the increased recovery of phosphatidylglycerol (r = -0.74, p < 0.03 and r = 0.94, p < 0.05, respectively). These results suggest that rhDNase is able to increase the free water content and alter the phospholipid profile of mucus, with a related improvement in CF mucus transportability.
Zahm
J M
JM
INSERM U314, IFR53, Reims; Hôpital Renée Sabran, Giens; and Laboratoire Roche, Neuilly, France.
Galabert
C
C
Chaffin
A
A
Chazalette
J P
JP
Grosskopf
C
C
Puchelle
E
E
D000328:Adult; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D003851:Deoxyribonucleases / Q000494:pharmacology*; D004548:Elasticity; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis; D008297:Male; D009079:Mucociliary Clearance; D009093:Mucus / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000032:analysis; D010743:Phospholipids / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014783:Viscosity
D008055:Lipids; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011994:Recombinant Proteins; D003851:Deoxyribonucleases