The UDP-sugar-sensing P2Y14 receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils
The G i -coupled P2Y 14 receptor (P2Y 14 -R) is potently activated by UDP-sugars and UDP. Although P2Y 14 -R mRNA is prominently expressed in circulating neutrophils, the signaling pathways and functional responses associated with this receptor are undefined. In this study, we illustrate that incuba...
Gespeichert in:
Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2012-09, Vol.303 (5), p.C490-C498 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The G
i
-coupled P2Y
14
receptor (P2Y
14
-R) is potently activated by UDP-sugars and UDP. Although P2Y
14
-R mRNA is prominently expressed in circulating neutrophils, the signaling pathways and functional responses associated with this receptor are undefined. In this study, we illustrate that incubation of isolated human neutrophils with UDP-glucose resulted in cytoskeleton rearrangement, change of cell shape, and enhanced cell migration. We also demonstrate that UDP-glucose promotes rapid, robust, and concentration-dependent activation of RhoA in these cells. Ecto-nucleotidases expressed on neutrophils rapidly hydrolyzed extracellular ATP, but incubation with UDP-glucose for up to 1 h resulted in negligible metabolism of the nucleotide-sugar. HL60 human promyelocytic leukemia cells do not express the P2Y
14
-R, but neutrophil differentiation of HL60 cells with DMSO resulted in markedly enhanced P2Y
14
-R expression. Accordingly, UDP-glucose, UDP-galactose, and UDP-
N
-acetylglucosamine promoted Rho activation in differentiated but not in undifferentiated HL60 cells. Stable expression of recombinant human P2Y
14
-R conferred UDP-sugar-promoted responses to undifferentiated HL60 cells. UDP-glucose-promoted RhoA activation also was accompanied by enhanced cell migration in differentiated HL60 cells, and these responses were blocked by Rho kinase inhibitors. These results support the notion that UDP-glucose is a stable and potent proinflammatory mediator that promotes P2Y
14
-R-mediated neutrophil motility via Rho/Rho kinase activation. |
---|---|
ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.00138.2012 |