PMID- 17827252
OWN - NLM
STAT- MEDLINE
DCOM- 20071220
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 293
IP  - 5
DP  - 2007 Nov
TI  - Unfractionated heparin reduces the elasticity of sputum from patients with cystic 
      fibrosis.
PG  - L1240-9
AB  - Mucus obstruction of the airway in patients with cystic fibrosis (CF) reduces 
      lung function, invites infection, and limits delivery of inhaled drugs including 
      gene therapy vectors to target cells. Not all patients respond to presently 
      available mucolytics, and new approaches are needed. Our objectives were to 
      investigate the in vitro effects of unfractionated heparin (UFH) on the 
      morphology and rheology of sputum and the effect of UFH on diffusion of 200-nm 
      nanospheres through sputum from adult CF patients. Confocal laser scanning 
      microscopy was used to image fluorescently stained actin and DNA components of CF 
      sputum, and atomic force microscopy was used to image isolated DNA networks. The 
      viscoelasticity of CF sputum was measured using dynamic oscillatory rheometry. 
      Nanosphere diffusion was measured through CF sputum using a Boyden chamber-based 
      assay. Actin-DNA bundles in CF sputum were disaggregated by UFH at concentrations 
      of 0.1-10 mg/ml, and UFH enhanced the endonuclease activity in sputum from 
      patients on dornase alfa therapy. UFH significantly reduced the elasticity and 
      yield stress, but not the viscosity, of CF sputum from patients not receiving 
      dornase alfa therapy. Heparin dose-dependently significantly increased the 
      diffusion of nanospheres through CF sputum from patients not on dornase alfa 
      therapy from 10.5 +/- 2.5% at baseline to 36.9 +/- 4.4% at 10 mg/ml but was more 
      potent, with maximal effect at 0.1 mg/ml, in patients who were on dornase alfa 
      therapy. Thus the mucoactive properties of UFH indicate its potential as a new 
      therapeutic approach in patients with cystic fibrosis.
FAU - Broughton-Head, Victoria J
AU  - Broughton-Head VJ
AD  - Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, 
      Portsmouth, UK.
FAU - Shur, Jagdeep
AU  - Shur J
FAU - Carroll, Mary P
AU  - Carroll MP
FAU - Smith, James R
AU  - Smith JR
FAU - Shute, Janis K
AU  - Shute JK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070907
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Adult
MH  - Cystic Fibrosis/*metabolism/pathology
MH  - Diffusion/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Elasticity
MH  - Electrophoresis, Agar Gel
MH  - Female
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Male
MH  - Microscopy, Atomic Force
MH  - Microscopy, Confocal
MH  - Microspheres
MH  - Mucociliary Clearance/*drug effects
MH  - Rheology/drug effects
MH  - Sputum/*metabolism
EDAT- 2007/09/11 09:00
MHDA- 2007/12/21 09:00
CRDT- 2007/09/11 09:00
PHST- 2007/09/11 09:00 [pubmed]
PHST- 2007/12/21 09:00 [medline]
PHST- 2007/09/11 09:00 [entrez]
AID - 00206.2007 [pii]
AID - 10.1152/ajplung.00206.2007 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2007 Nov;293(5):L1240-9. doi: 
      10.1152/ajplung.00206.2007. Epub 2007 Sep 7.