P2X1 Ion Channels Promote Neutrophil Chemotaxis through Rho Kinase Activation
Open Access
- 14 August 2009
- journal article
- research article
- Published by The American Association of Immunologists in Journal Of Immunology
- Vol. 183 (4), 2801-2809
- https://doi.org/10.4049/jimmunol.0804007
Abstract
ATP, released at the leading edge of migrating neutrophits, 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, alpha beta-methylene ATP (alpha beta MeATP) and beta gamma MeATP. These currents were strongly impaired or absent in neutrophils from P2X(1)(-/-) mice. In Boyden chamber assays, alpha beta MeATP 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, alpha beta MeATP selectively activated the small RhoGTPase RhoA that caused reversible myosin L chain phosphorylation. Moreover, the alpha beta MeATP-elicited neutrophil movements were prevented by the two Rho kinase inhibitors, Y27632 and H1152. In a gradient of W-peptide, P2X(1)(-/-) neutrophits 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 alpha beta MeATP, 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. The Journal of Immunology, 2009, 183: 2801-2809.This publication has 55 references indexed in Scilit:
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