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

Lohman, A. W. et al. (2015) Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation. Nature Communications, 6, 7965. (doi: 10.1038/ncomms8965) (PMID:26242575) (PMCID:PMC4824045)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Johnstone, Dr Scott
Authors: Lohman, A. W., Leskov, I. L., Butcher, J. T., Johnstone, S. R., Stokes, T. A., Begandt, D., DeLalio, L. J., Best, A. K., Penuela, S., Leitinger, N., Ravichandran, K. S., Stokes, K. Y., and Isakson, B. E.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2015 Macmillan Publishers Limited.
First Published:First published in Nature Communications 6:7965
Publisher Policy:Reproduced under a Creative Commons License

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