Purinergic signaling: a fundamental mechanism in neutrophil activation.
Authors:
Journal: Science signaling
Publication Type: Journal Article
Date: 2010
DOI: NIHMS548072
ID: 20530802
Abstract
Efficient activation of neutrophils is a key requirement for effective immune responses. We found that neutrophils released cellular adenosine triphosphate (ATP) in response to exogenous stimuli such as formylated bacterial peptides and inflammatory mediators that activated Fcgamma, interleukin-8, C5a complement, and leukotriene B(4) receptors. Stimulation of the formyl peptide receptor (FPR) led to ATP release through pannexin-1 (panx1) hemichannels, and FPRs colocalized with P2Y2 nucleotide receptors on the cell surface to form a purinergic signaling system that facilitated neutrophil activation. Disruption of this purinergic signaling system by inhibiting or silencing panx1 hemichannels or P2Y2 receptors blocked neutrophil activation and impaired innate host responses to bacterial infection. Thus, purinergic signaling is a fundamental mechanism required for neutrophil activation and immune defense.
Chemical List
- Receptors, Purinergic|||Adenosine Triphosphate
Reference List
- Nussler AK, Wittel UA, Nussler NC, Beger HG. Leukocytes, the Janus cells in inflammatory disease. Langenbecks Arch Surg. 1999;384:222–232.|||Rabiet MJ, Huet E, Boulay F. The N-formyl peptide receptors and the anaphylatoxin C5a receptors: an overview. Biochimie. 2007;89:1089–1106.|||Waugh J, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res. 2008;14:6735–6741.|||Capra V. Molecular and functional aspects of human cysteinyl leukotriene receptors. Pharmacol Res. 2004;50:1–11.|||Fuller SJ, Stokes L, Skarratt KK, Gu BJ, Wiley JS. Genetics of the P2X7 receptor and human disease. Purinergic Signal. 2009;5:257–262.|||Di Virgilio F, Ceruti S, Bramanti P, Abbracchio MP. Purinergic signalling in inflammation of the central nervous system. Trends Neurosci. 2009;32:79–87.|||Qu Y, Ramachandra L, Mohr S, Franchi L, Harding CV, Nunez G, Dubyak GR. P2X7 receptor-stimulated secretion of MHC class II-containing exosomes requires the ASC/NLRP3 inflammasome but is independent of caspase-1. J Immunol. 2009;182:5052–5062.|||Hasko G, Linden J, Crostein B, Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008;7:759–770.|||Fredholm BB. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ. 2007;14:1315–1323.|||Burnstock G, Knight GE. Cellular distribution and functions of P2 receptor subtypes in different systems. Int Tev Cytol. 2004;240:31–304.|||Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev. 2001;53:527–552.|||Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science. 2006;314:1792–1795.|||Schwiebert M. ATP release mechanisms, ATP receptors and purinergic signalling along the nephron. Clin Exp Pharmacol Physiol. 2001;28:340–350.|||Eltzschig K, Eckle T, Mager A, Kuper N, Karcher C, Weissmuller T, Boengler K, Schulz R, Robson SC, Colgan SP. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res. 2006;99:1100–1108.|||Suzuki M, Mizuno A. A novel human Cl(-) channel family related to Drosophila flightless locus. J Biol Chem. 2004;279:22461–22468.|||Schenk U, Westendorf AM, Radaelli E, Casati A, Ferro M, Fumagalli M, Verderio C, Buer J, Scanziani E, Grassi F. Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci Signal. 2008;1:ra6.|||Sabirov RZ, Okada Y. ATP release via anion channels. Purinergic Signal. 2005;1:311–328.|||Ma W, Hui H, Pelegrin P, Surprenant A. Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. J Pharmacol Exp Ther. 2009;328:409–418.|||Leite MS, Thomaz R, Oliveira JH, Oliveira PL, Meyer-Fernandes JR. Trypanosoma brucei brucei: effects of ferrous iron and heme on ecto-nucleoside triphosphate diphosphohydrolase activity. Exp Parasitol. 2009;121:137–143.|||Chen Y, Hashiguchi N, Yip L, Junger WG. Hypertonic saline enhances neutrophil elastase release through activation of P2 and A3 receptors. Am J Physiol Cell Physiol. 2006;290:C1051–1059.|||Pelegrin P, Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J. 2006;25:5071–5082.|||Corriden R, Chen Y, Inoue Y, Beldi G, Robson SC, Insel PA, Junger WJ. Ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1/CD39) regulates neutrophil chemotaxis by hydrolyzing released ATP to adenosine. J Biol Chem. 2008;283:28480–28486.|||Thompson RJ, Jackson MF, Olah ME, Rungta RL, Hines DJ, Beazely MA, MacDonald JF, MacVicar BA. Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus. Science. 2008;322:1555–1559.|||Inoue Y, Chen Y, Hirsh MI, Yip L, Junger WG. A3 and P2Y2 receptors control the recruitment of neutrophils to the lungs in a mouse model of sepsis. Shock. 2008;30:173–177.|||Weiss SJ. Tissue destruction by neutrophils. N Engl J Med. 1989;320:365–376.|||Bodin P, Burnstock G. Purinergic signalling: ATP release. Neurochem Res. 2001;26:959–969.|||Bao L, Locovei S, Dahl G. Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 2004;572:65–68.|||Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M. Connexin 43 hemichannels are permeable to ATP. J Neurosci. 2008;28:4702–4711.|||Bell D, Lapointe JY, Sabirov R, Hayashi S, Peti-Peterdi J, Manabe K-I, Kovacs G, Okada Y. Macula densa cell signaling involves ATP release through a maxi anion channel. Proc Natl Acad Sci U S A. 2003;100:4322–4327.|||Dutta K, Sabirov RZ, Uramoto H, Okada Y. Role of ATP-conductive anion channel in ATP release from neonatal rat cardiomyocytes in ischaemic or hypoxic conditions. J Physiol. 2004;559:799–812.|||Dutta K, Korchev YE, Shevchuk AI, Hayashi S, Okada Y, Sabirov RZ. Spatial distribution of maxi-anion channel on cardiomyocytes detected by smart-patch technique. Biophys J. 2008;94:1646–1655.|||Sabirov Z, Dutta AK, Okada Y. Volume-dependent ATP-conductive large-conductance anion channel as a pathway for swelling-induced ATP release. J Gen Physiol. 2001;118:251–266.|||Liu HT, Tashmukhamedov BA, Inoue H, Okada Y, Sabirov RZ. Roles of two types of anion channels in glutamate release from mouse astrocytes under ischemic or osmotic stress. Glia. 2006;54:343–357.|||Ram A, Singh SK, Singh VP, Kumar S, Ghosh B. Inhaled carbenoxolone prevents allergic airway inflammation and airway hyperreactivity in a mouse model of asthma. Int Arch Allergy Immunol. 2009;149:38–46.|||Bai M. Dimerization of G-protein-coupled receptors: roles in signal transduction. Cell Signal. 2004;16:175–186.|||Franco R, Casado V, Cortes A, Mallol J, Ciruela F, Ferre S, Lluis C, Canela EI. G-protein-coupled receptor heteromers: function and ligand pharmacology. Br J Pharmacol. 2008;153(Suppl 1):S90–98.|||Franco R, Ferre S, Agnati L, Torvinen M, Gines S, Hillion J, Casado V, Lledo P, Zoli M, Lluis C, Fuxe K. Evidence for adenosine/dopamine receptor interactions: indications for heteromerization. Neuropsychopharmacology. 2000;23:S50–59.|||Yoshioka K, Saitoh O, Nakata H. Heteromeric association creates a P2Y-like adenosine receptor. Proc Natl Acad Sci U S A. 2001;98:7617–7622.|||Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008;1782:673–694.|||Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park RI, Woodson D, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461:181–182.|||Relvas LJ, Bouffioux C, Marcet B, Communi D, Makhoul M, Horckmans M, Blero C, Bruyns D, Caspers L, Boeynaems JM, Willermain F. Extracellular nucleotides and interleukin-8 production by ARPE cells: potential role of danger signals in blood-retinal barrier activation. Invest Ophthalmol Vis Sci. 2009;50:1241–1246.|||Junger WG, Hoyt DB, Davis RE, Herdon-Remelius C, Namiki S, Junger H, Loomis W, Altman A. Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38. J Clin Invest. 1998;101:2768–2779.