Extracellular adenosine triphosphate and chronic obstructive pulmonary disease.
BACKGROUND
Extracellular ATP promotes inflammation, but its role in chronic obstructive pulmonary disease (COPD) is unknown.


OBJECTIVE
To analyze the expression of ATP and its functional consequences in never-smokers, asymptomatic smokers, and patients with COPD.


METHODS
ATP was quantified in bronchoalveolar lavage fluid (BALF) of never-smokers, asymptomatic smokers, and patients with COPD of different severity. The expression of specific ATP (purinergic) receptors was measured in airway macrophages and blood neutrophils from control subjects and patients with COPD. The release of mediators by macrophages and neutrophils and neutrophil chemotaxis was assessed after ATP stimulation.


RESULTS
Chronic smokers had elevated ATP concentrations in BALF compared with never-smokers. Acute smoke exposure led to a further increase in endobronchial ATP concentrations. Highest ATP concentrations in BALF were present in smokers and ex-smokers with COPD. In patients with COPD, BALF ATP concentrations correlated negatively with lung function and positively with BALF neutrophil counts. ATP induced a stronger chemotaxis and a stronger elastase release in blood neutrophils from patients with COPD, as compared with control subjects. In addition, airway macrophages from patients with COPD responded with an increased secretion of proinflammatory and tissue-degrading mediators after ATP stimulation. These findings were accompanied by an up-regulation of specific purinergic receptors in blood neutrophils and airway macrophages of patients with COPD.


CONCLUSIONS
COPD is characterized by a strong and persistent up-regulation of extracellular ATP in the airways. Extracellular ATP appears to contribute to the pathogenesis of COPD by promoting inflammation and tissue degradation.
Lommatzsch
Marek
M
Department of Pneumology, University of Rostock, Rostock, Germany.
Cicko
Sanja
S
Müller
Tobias
T
Lucattelli
Monica
M
Bratke
Kai
K
Stoll
Paul
P
Grimm
Melanie
M
Dürk
Thorsten
T
Zissel
Gernot
G
Ferrari
Davide
D
Di Virgilio
Francesco
F
Sorichter
Stephan
S
Lungarella
Giuseppe
G
Virchow
J Christian
JC
Idzko
Marco
M
D000255:Adenosine Triphosphate / Q000032:analysis*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D045604:Extracellular Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000032:analysis; D012507:Sarcoidosis / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate