P2X1 Ion Channels Promote Neutrophil Chemotaxis through Rho Kinase Activation

C. Lecut, K. Frederix, D. M. Johnson, C. Deroanne, M. Thiry, C. Faccinetto, R. Maree, R. J. Evans, P. G. A. Volders, V. Bours, Cecile Oury

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70 Citations (Scopus)


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 P2X1 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 P2X1 agonists, αβ-methylene ATP (αβMeATP) and βγMeATP. These currents were strongly impaired or absent in neutrophils from P2X1−/− mice. In Boyden chamber assays, αβMeATP 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 P2X1−/− neutrophils. In human as in mouse neutrophils, αβMeATP selectively activated the small RhoGTPase RhoA that caused reversible myosin L chain phosphorylation. Moreover, the αβMeATP-elicited neutrophil movements were prevented by the two Rho kinase inhibitors, Y27632 and H1152. In a gradient of W-peptide, P2X1−/− 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 αβMeATP, whereas it was significantly impaired in the P2X1−/− mice. Thus, activation of P2X1 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.
Original languageEnglish
Pages (from-to)2801-2809
JournalJournal of Immunology
Issue number4
Publication statusPublished - Aug 2009


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