@article{1990f7af7b4d4acaa648baa6e79fa816,
title = "Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation",
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 P 2 Y 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.",
author = "Lohman, {Alexander W.} and Leskov, {Igor L.} and Butcher, {Joshua T.} and Johnstone, {Scott R.} and Stokes, {Tara A.} and Daniela Begandt and Delalio, {Leon J.} and Best, {Angela K.} and Silvia Penuela and Norbert Leitinger and Ravichandran, {Kodi S.} and Stokes, {Karen Y.} and Isakson, {Brant E.}",
note = "Funding Information: We would like to thank Dr Ralf Adams (Max Plank Institute, Germany) for the generous gift of the VECadERT2+ mice. We would also like to acknowledge the University of Virginia Histology core for processing vessels for sectioning and mounting. We thank the the animal core, part of HL120840, for help in breeding some of the VECadERT2+/ Panx1fl/fl mice. The Zeiss Sigma VPHD Field Emission Scanning Electron Microscope was purchased with NIH S10 grant funding. This work was supported by National Institutes of Health grants HL088554 (B.E.I.), HL107963 (B.E.I.), GM107848 (K.S.R.), P01 HL120840 (K.S.R., B.E.I., N.L.) National Institute of General Medical Sciences grant 8P20GM103433 (K.Y.S.) and an American Heart Association predoctoral ellowship (A.W.L.).",
year = "2015",
month = aug,
day = "5",
doi = "10.1038/ncomms8965",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
}