title: 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 P2Y14receptors (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.
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina School of Medicine, 6007 Thurston-Bowles Building, CB 7248, Chapel Hill, NC, 27599-7248, USA.
authors.forename: Juliana I
authors.initials: JI
authors.lastname: Sesma
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Clarissa D
authors.initials: CD
authors.lastname: Weitzer
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina School of Medicine, 6007 Thurston-Bowles Building, CB 7248, Chapel Hill, NC, 27599-7248, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Livraghi-Butrico
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina School of Medicine, 6007 Thurston-Bowles Building, CB 7248, Chapel Hill, NC, 27599-7248, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Dang
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina School of Medicine, 6007 Thurston-Bowles Building, CB 7248, Chapel Hill, NC, 27599-7248, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Donaldson
authors.affiliation: Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: T Kendall
authors.initials: TK
authors.lastname: Harden
authors.affiliation: Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina School of Medicine, 6007 Thurston-Bowles Building, CB 7248, Chapel Hill, NC, 27599-7248, USA. eduardo_lazarowski@med.unc.edu.
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Lazarowski
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000818:Animals; D003550:Cystic Fibrosis / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013183:Sputum / Q000276:immunology / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000276:immunology; D014532:Uridine Diphosphate Glucose / Q000378:metabolism / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D000255:Adenosine Triphosphate; D014532:Uridine Diphosphate Glucose
keywords: Lung inflammation; Neutrophils; P2Y14 receptor; Purinergic receptors; UDP-glucose