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Nat Commun. 2015 Aug 5;6:7965. doi: 10.1038/ncomms8965.

Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation.

Author information

1
1] Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA [2] Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
2
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Los Angeles 71130, USA.
3
Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
4
British Heart Foundation Cardiovascular Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
5
1] Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA [2] Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
6
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 5C1.
7
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
8
Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.

Abstract

Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by a plethora of signalling processes influencing cell-to-cell interactions between the vascular endothelial cells (ECs) in post-capillary venules and circulating leukocytes. Recently, ATP-sensitive P2Y purinergic receptors have emerged as downstream regulators of EC activation in vascular inflammation. However, the mechanism(s) regulating cellular ATP release in this response remains elusive. Here we report that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α. This process involves activation of type-1 TNF receptors, recruitment of Src family kinases (SFK) and SFK-dependent phosphorylation of Panx1. Using an inducible, EC-specific Panx1 knockout mouse line, we report a previously unidentified role for Panx1 channels in promoting leukocyte adhesion and emigration through the venous wall during acute systemic inflammation, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.

PMID:
26242575
PMCID:
PMC4824045
DOI:
10.1038/ncomms8965
[Indexed for MEDLINE]
Free PMC Article

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