UDP-glucose promotes neutrophil recruitment in the lung
| Autor: | Juliana I. Sesma, Scott H. Donaldson, Clarissa D. Weitzer, Eduardo R. Lazarowski, Hong Dang, Kenneth A. Jacobson, Alessandra Livraghi-Butrico, T. Kendall Harden, Neil E. Alexis |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Uridine Diphosphate Glucose P2Y receptor Cystic Fibrosis Neutrophils Cell Inflammation Pharmacology Cystic fibrosis 03 medical and health sciences Cellular and Molecular Neuroscience Mice Young Adult 0302 clinical medicine Adenosine Triphosphate medicine Animals Humans Receptor Molecular Biology Lung Chemistry Purinergic receptor Sputum Cell Biology medicine.disease Pathophysiology Trachea carbohydrates (lipids) Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neutrophil Infiltration Immunology Cytokines Female Original Article medicine.symptom 030217 neurology & neurosurgery |
| DOI: | 10.17615/qb3w-2y38 |
| Popis: | 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 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 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. |
| Databáze: | OpenAIRE |
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