Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3

Fausther, Michel; Pelletier, Julie; Ribeiro, Carla M. P.; Sévigny, Jean; Picher, Maryse

doi:10.1152/ajplung.00019.2010

Cited by 22 publications

(14 citation statements)

References 77 publications

(112 reference statements)

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“…1). Ecto-nucleotidases expressed on (or secreted/shed from) epithelial cells and inflammatory cells [29,39,40] could have contributed to the pattern of nucleotide accumulation observed in control and CF sputum. To gain an insight into potential metabolism differences between ATP and UDPglucose in lung secretions, rates of ATP and UDP-glucose hydrolysis were assessed in sputum supernatants.…”

Section: Resultsmentioning

confidence: 99%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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In addition to their role in glycosylation reactions, UDP-sugars are released from cells and activate widely distributed cell surface P2Y 14 receptors (P2Y 14 R). However, the physiological/pathophysiological consequences of UDPsugar release are incompletely defined. Here, we report that UDP-glucose levels are abnormally elevated in lung secretions from patients with cystic fibrosis (CF) as well as in a mouse model of CF-like disease, the βENaC transgenic (Tg) mouse. Instillation of UDP-glucose into wild-type mouse tracheas resulted in enhanced neutrophil lung recruitment, and this effect was nearly abolished when UDP-glucose was coinstilled with the P2Y 14 R antagonist PPTN [4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl-2-naphthoic acid]. Importantly, administration of PPTN to βENaC-Tg mice reduced neutrophil lung inflammation. These results suggest that UDP-glucose released into the airways acts as a local mediator of neutrophil inflammation.

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Section: Resultsmentioning

confidence: 99%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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“…NTPDase1/CD39 is expressed in human epithelial cells, playing a role in the regulation of leukocyte infiltration [38]. In the human study we measured CD39 expression and ATPase activity in sputum and BALF inflammatory cells, but not in airway epithelium.…”

Section: Discussionmentioning

confidence: 99%

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD

et al. 2015

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Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smokeinduced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage. @ERSpublications The upregulation of pulmonary ATPase is a protective mechanism in cigarette smoke-induced lung inflammation http://ow.ly/S5YcC

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“…NTPDase3 was located in a subclass of neurons in the rat brain (3) and in epithelial cells of the human pulmonary (17) and murine reproductive systems (36). In the reproductive system, NTPDase3 expression is limited to epithelial cells of the seminal vesicle, epididymis (principal cells), oviduct, and secretory epithelia of the prostate and Cowper's gland (36).…”

Section: Discussionmentioning

confidence: 99%

Ectonucleotidases in the digestive system: focus on NTPDase3 localization

Lavoie

Gulbransen

Martı́n-Satué

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Extracellular nucleotides and adenosine are biologically active molecules that bind members of the P2 and P1 receptor families, respectively. In the digestive system, these receptors modulate various functions, including salivary, gastric, and intestinal epithelial secretion and enteric neurotransmission. The availability of P1 and P2 ligands is modulated by ectonucleotidases, enzymes that hydrolyze extracellular nucleotides into nucleosides. Nucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase are the dominant ectonucleotidases at physiological pH. While there is some information about the localization of ecto-5'-nucleotidase and NTPDase1 and -2, the distribution of NTPDase3 in the digestive system is unknown. We examined the localization of these ectonucleotidases, with a focus on NTPDase3, in the gastrointestinal tract and salivary glands. NTPDase1, -2, and -3 are responsible for ecto-ATPase activity in these tissues. Semiquantitative RT-PCR, immunohistochemistry, and in situ enzyme activity revealed the presence of NTPDase3 in some epithelial cells in serous acini of salivary glands and mucous acini and duct cells of sublingual salivary glands, in cells from the stratified esophageal and forestomach epithelia, and in some enteroendocrine cells of the gastric antrum. Interestingly, NTPDase2 and ecto-5'-nucleotidase are coexpressed with NTPDase3 in salivary gland cells and stratified epithelia. In the colon, neurons express NTPDase3 and glial cells express NTPDase2. Ca(2+) imaging experiments demonstrate that NTPDases regulate P2 receptor ligand availability in the enteric nervous system. In summary, the specific localization of NTPDase3 in the digestive system suggests functional roles of the enzyme, in association with NTPDase2 and ecto-5'-nucleotidase, in epithelial functions such as secretion and in enteric neurotransmission.

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Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3

Cited by 22 publications

References 77 publications

UDP-glucose promotes neutrophil recruitment in the lung

UDP-glucose promotes neutrophil recruitment in the lung

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD

Ectonucleotidases in the digestive system: focus on NTPDase3 localization

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