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UDP-glucose promotes neutrophil recruitment in the lung.

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.
AuthorsJuliana I Sesma, Clarissa D Weitzer, Alessandra Livraghi-Butrico, Hong Dang, Scott Donaldson, Neil E Alexis, Kenneth A Jacobson, T Kendall Harden, Eduardo R Lazarowski
JournalPurinergic signalling (Purinergic Signal) Vol. 12 Issue 4 Pg. 627-635 (12 2016) ISSN: 1573-9546 [Electronic] Netherlands
PMID27421735 (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.)
Chemical References
  • Cytokines
  • Adenosine Triphosphate
  • Uridine Diphosphate Glucose
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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