Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation.
Alexander W. Lohman,Igor L. Leskov,Joshua T. Butcher,Scott R. Johnstone,Tara A. Stokes,Daniela Begandt,Leon J. DeLalio,Angela K. Best,Silvia Penuela,Norbert Leitinger,Kodi S. Ravichandran,Karen Y. Stokes,Brant E. Isakson +12 more
TLDR
It is reported that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.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.read more
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Purinergic Signaling in the Cardiovascular System.
TL;DR: The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine.
Journal ArticleDOI
TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue.
Peng Zhao,Kai in Wong,Xiaoli Sun,Shannon M. Reilly,Shannon M. Reilly,Maeran Uhm,Zhongji Liao,Yuliya Skorobogatko,Yuliya Skorobogatko,Alan R. Saltiel,Alan R. Saltiel +10 more
TL;DR: It is reported that the kinase uniquely controls energy metabolism, and a unique role for TBK1 in mediating bidirectional crosstalk between energy sensing and inflammatory signaling pathways in both over- and undernutrition.
Journal ArticleDOI
Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications
Luc Leybaert,Paul D. Lampe,Stefan Dhein,Brenda R. Kwak,Péter Ferdinandy,Eric C. Beyer,Dale W. Laird,Christian C. Naus,Colin R. Green,Rainer Schulz +9 more
TL;DR: It is concluded that peptide-based investigations have raised several new opportunities for interfering with connexins and their channels that may soon allow preservation of gap junction communication, inhibition of hemichannel opening, and mitigation of inflammatory signaling.
Journal ArticleDOI
Mechanisms of ATP Release by Inflammatory Cells
TL;DR: Key effector functions of inflammatory cells are regulated by purinergic signaling in acute and chronic diseases, making extracellular nucleotide release a promising target for the development of new therapies.
Journal ArticleDOI
ATP Release Channels.
TL;DR: Five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR) anion channel), and maxi-anion channels(MACs), and a discussion on the future implications of understanding these channels are summarized.
References
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Journal ArticleDOI
Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP
TL;DR: How atp and other nucleotides are released from intact cells is a fundamental question, given the existence of multiple purinergic receptor signaling cascades operative in most vertebrate tissues.
Journal ArticleDOI
TNFα induces survival through the FLIP-L-dependent activation of the MAPK/ERK pathway.
Fernando Marqués-Fernández,Laura Planells-Ferrer,Raffaella Gozzelino,K Mo Galenkamp,Stephanie Reix,Nuria Llecha-Cano,Joaquín López-Soriano,Victor J. Yuste,Rana S. Moubarak,Joan X. Comella +9 more
TL;DR: A previously undescribed and essential role for MAPK/ERK activation by FLIP-L in the decision between cell survival and apoptosis upon TNFα stimulation is reported.
Journal ArticleDOI
P2Y2 Receptor Regulates VCAM-1 Membrane and Soluble Forms and Eosinophil Accumulation during Lung Inflammation
Gilles Vanderstocken,Benjamin Bondue,Michael Horckmans,Larissa Di Pietrantonio,Bernard Robaye,Jean-Marie Boeynaems,Didier Communi +6 more
TL;DR: In this article, the authors evaluated lung inflammation in mice deficient for the P2Y(2) purinergic receptor and observed that eosinophil accumulation, a distinctive feature of lung allergic inflammation, was defective in OVA-treated P2y(2)-deficient mice compared with wild type animals.
Journal ArticleDOI
Involvement of Native TRPC3 Proteins in ATP-Dependent Expression of VCAM-1 and Monocyte Adherence in Coronary Artery Endothelial Cells
TL;DR: Findings indicate that in HCAECs, native TRPC3 proteins form channels that contribute to constitutive and ATP-dependent Ca2+ influx, and that TRPC 3 expression and function are fundamental to support VCAM-1 expression and monocyte binding.
Journal ArticleDOI
Nitric oxide modulation of neutrophil-endothelium interaction: difference between arterial and venous coronary bypass grafts.
TL;DR: The lesser neutrophil adhesion to the endothelium of the IMA is a consequence of enhanced release of NO at this level; this effect could be responsible for the better early and long-term patency of this conduit over the SVG in coronary bypass grafting.
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