Abstract |
In addition to their role in glycosylation reactions, UDP-sugars are released from cells and activate widely distributed cell surface P2Y14 receptors (P2Y14R). However, the physiological/pathophysiological consequences of UDP- sugar 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 co-instilled with the P2Y14R 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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Authors | Juliana I Sesma, Clarissa D Weitzer, Alessandra Livraghi-Butrico, Hong Dang, Scott Donaldson, Neil E Alexis, Kenneth A Jacobson, T Kendall Harden, Eduardo R Lazarowski |
Journal | Purinergic signalling
(Purinergic Signal)
Vol. 12
Issue 4
Pg. 627-635
(12 2016)
ISSN: 1573-9546 [Electronic] Netherlands |
PMID | 27421735
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Cytokines
- Adenosine Triphosphate
- Uridine Diphosphate Glucose
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Topics |
- Adenosine Triphosphate
(metabolism)
- Adult
- Animals
- Cystic Fibrosis
(immunology, metabolism)
- Cytokines
(metabolism)
- Disease Models, Animal
- Female
- Humans
- Lung
(drug effects, immunology, metabolism)
- Male
- Mice
- Neutrophil Infiltration
(drug effects)
- Neutrophils
(drug effects, immunology, metabolism)
- Sputum
(immunology, metabolism)
- Trachea
(drug effects, immunology)
- Uridine Diphosphate Glucose
(metabolism, pharmacology)
- Young Adult
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