Published online before print
February 6, 2008 Eur Respir J 2008, doi:10.1183/09031936.00089807
Extracellular Purines are Biomarkers of Neutrophilic Airway Inflammation
C.R. Esther 1*,
N.E. Alexis 2,
M.L. Clas 1,
E.R. Lazarowski 3,
S.H. Donaldson 3,
C.M. Pedrosa Ribeiro 3,
C.G. Moore 4,
S.D. Davis 1,
R.C. Boucher 3
1 paediatric Pulmonology
2 CEMALB
3 CF Research Center
4 Division of General Medicine and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
* To whom correspondence should be addressed. E-mail: Charles_Esther{at}med.unc.edu.
 |
Abstract |
|---|
Purinergic signaling regulates airway defense mechanisms, suggesting that extracellular purines could serve as airway inflammation biomarkers in cystic fibrosis (CF). The purines ATP, ADP, AMP, and adenosine were measured in sputum from 21 adults (spontaneously expectorated from 7 CF, induced from 14 healthy controls) to assess normal values and CF associated changes. Subsequently, purine levels were measured in bronchoalveolar lavage fluid (BALF) from 37 children (25 CF, 12 disease controls) and compared to neutrophilic counts, presence of airway infection, and lung function. To non-invasively assess airway purines, ATP levels were measured using luminometry in exhaled breath condensate (EBC) from 14 children with CF and 14 healthy controls, then 14 CF children during a pulmonary exacerbation. Both ATP and AMP were elevated in sputum and BALF from CF subjects compared to controls. In BALF, ATP and AMP levels were inversely related to lung function and strongly correlated with neutrophil counts. In EBC, ATP levels were increased in CF relative to controls and decreased after treatment of CF pulmonary exacerbation. The purines ATP and AMP are candidate biomarkers of neutrophilic airways inflammation. Measurement of purines in sputum or EBC may provide a relatively simple and non-invasive method to track this inflammation.
Keywords:
Biomarker, bronchoalveolar lavage fluid, cystic fibrosis, exhaled breath condensate, inflammation, purinergic signaling
This article has been cited by other articles:

|
 |

|
 |
 
I. Horvath, Z. Lazar, N. Gyulai, M. Kollai, and G. Losonczy
Exhaled biomarkers in lung cancer
Eur. Respir. J.,
July 1, 2009;
34(1):
261 - 275.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Esther Jr., G. Boysen, B. M. Olsen, L. B. Collins, A. J. Ghio, J. W. Swenberg, and R. C. Boucher
Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis
Am J Physiol Lung Cell Mol Physiol,
June 1, 2009;
296(6):
L987 - L993.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. I. Sesma, C. R. Esther Jr., S. M. Kreda, L. Jones, W. O'Neal, S. Nishihara, R. A. Nicholas, and E. R. Lazarowski
Endoplasmic Reticulum/Golgi Nucleotide Sugar Transporters Contribute to the Cellular Release of UDP-sugar Signaling Molecules
J. Biol. Chem.,
May 1, 2009;
284(18):
12572 - 12583.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Makam, D. Diaz, J. Laval, Y. Gernez, C. K. Conrad, C. E. Dunn, Z. A. Davies, R. B. Moss, L. A. Herzenberg, L. A. Herzenberg, et al.
Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs
PNAS,
April 7, 2009;
106(14):
5779 - 5783.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. C. Denlinger, L. Shi, A. Guadarrama, K. Schell, D. Green, A. Morrin, K. Hogan, R. L. Sorkness, W. W. Busse, and J. E. Gern
Attenuated P2X7 Pore Function as a Risk Factor for Virus-induced Loss of Asthma Control
Am. J. Respir. Crit. Care Med.,
February 15, 2009;
179(4):
265 - 270.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. McClenahan, K. Hillenbrand, A. Kapur, D. Carlton, and C. Czuprynski
Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities
Clin. Vaccine Immunol.,
January 1, 2009;
16(1):
43 - 48.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2008 by the European Respiratory Society.
|