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Title: P2X1 ion channels promote neutrophil chemotaxis through Rho kinase activation
Authors: Lecut, Christelle ×
Frederix, Kim
Johnson, Daniel M #
Deroanne, Christophe
Thiry, Marc
Faccinetto, Céline
Marée, Raphaël
Evans, Richard J
Volders, Paul G A
Bours, Vincent
Oury, Cécile #
Issue Date: Aug-2009
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:183 issue:4 pages:2801-9
Article number: 10.4049/jimmunol.0804007
Abstract: ATP, released at the leading edge of migrating neutrophils, amplifies chemotactic signals. The aim of our study was to investigate whether neutrophils express ATP-gated P2X(1) ion channels and whether these channels could play a role in chemotaxis. Whole-cell patch clamp experiments showed rapidly desensitizing currents in both human and mouse neutrophils stimulated with P2X(1) agonists, alphabeta-methylene ATP (alphabetaMeATP) and betagammaMeATP. These currents were strongly impaired or absent in neutrophils from P2X(1)(-/-) mice. In Boyden chamber assays, alphabetaMeATP provoked chemokinesis and enhanced formylated peptide- and IL-8-induced chemotaxis of human neutrophils. This agonist similarly increased W-peptide-induced chemotaxis of wild-type mouse neutrophils, whereas it had no effect on P2X(1)(-/-) neutrophils. In human as in mouse neutrophils, alphabetaMeATP selectively activated the small RhoGTPase RhoA that caused reversible myosin L chain phosphorylation. Moreover, the alphabetaMeATP-elicited neutrophil movements were prevented by the two Rho kinase inhibitors, Y27632 and H1152. In a gradient of W-peptide, P2X(1)(-/-) neutrophils migrated with reduced speed and displayed impaired trailing edge retraction. Finally, neutrophil recruitment in mouse peritoneum upon Escherichia coli injection was enhanced in wild-type mice treated with alphabetaMeATP, whereas it was significantly impaired in the P2X(1)(-/-) mice. Thus, activation of P2X(1) ion channels by ATP promotes neutrophil chemotaxis, a process involving Rho kinase-dependent actomyosin-mediated contraction at the cell rear. These ion channels may therefore play a significant role in host defense and inflammation.
URI: 
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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