Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?

Abstract

High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.

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Deller, M. , Mathioudakis, D. , Engel, J. , Dehne, M. , Wolff, M. , Fuchs, M. , Scheffer, G. and Mühling, J. (2014) Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?. Open Journal of Immunology, 4, 157-174. doi: 10.4236/oji.2014.44018.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Frei, J., Aellig, A. and Nessi, P. (1975) Enzyme System and Coenzymes Involved in the Energy Metabolism of Leukocytes. Function and Metabolism of Polymorphonuclear Neutrophils. Annales de Biologie Clinique (Paris), 33, 459-464.
[2] Frei, J. and Jemelin, M. (1972) Metabolism of Leukocytes in Health and Disease. Introduction, an Approach to Direct Metabolic Studies in Man. Enzyme, 13, 3-6.
[3] Frei, J., Maillard, M., Markert, M. and Aellig, M. (1980) Energetic Metabolism of Leukocytes. XI. Presence and Function of Creatine Kinase in Leukocytes. Enzyme, 25, 258-264.
[4] Jambunathan, P. and Zhang, K. (2014) Novel Pathways and Products from 2-Keto Acids. Current Opinion in Biotechnology, 29c, 1-7.
http://dx.doi.org/10.1016/j.copbio.2014.01.008
[5] Mühling, J., Nickolaus, K.A., Halabi, M., Fuchs, M. and Krüll, M. (2005) Alterations in Neutrophil (PMN) Free Intracellular Alpha-Keto Acid Profiles and Immune Functions Induced by L-Alanyl-L-Glutamine, Arginine or Taurine. Amino Acids, 29, 289-300.
http://dx.doi.org/10.1007/s00726-005-0223-8
[6] Mühling, J., Tussing, F., Nickolaus, K.A., Matejec, R. and Henrich, M. (2010) Effects of Alpha-Ketoglutarate on Neutrophil Intracellular Amino and Alpha-Keto Acid Profiles and ROS Production. Amino Acids, 38, 167-177.
http://dx.doi.org/10.1007/s00726-008-0224-5
[7] Markert, M. and Frei, J. (1978) Energy Metabolism of Polymorphonuclear Neutrophils and Phagocytosis (Proceedings). Annales de Biologie Clinique (Paris), 36, 201-204.
[8] Stjernholm, R.L., Burns, C.P. and Hohnadel, J.H. (1972) Carbohydrate Metabolism by Leukocytes. Enzyme, 13, 7-31.
[9] Stjernholm, R.L., Dimitrov, N.V. and Pijanowski, L.J. (1969) Carbohydrate Metabolism in Leukocytes. IX. Citric Acid Cycle Activity in Human Neutrophils. Journal of the Reticuloendothelial Society, 6, 194-201.
[10] Sznajd, J., Malkiewicz-Wasowicz, B., Naskalski, J. and Lisiewicz, J. (1972) Biochemistry of Normal and Leukemic Leukocytes. X. Energy and Carbohydrate Metabolism of Neutrophilic Granulocytes. Przegl Lek, 29, 634-640.
[11] He, G., Jiang, Y., Zhang, B. and Wu, G. (2014) The Effect of HIF-1α on Glucose Metabolism, Growth and Apoptosis of Pancreatic Cancerous Cells. Asia Pacific Journal of Clinical Nutrition, 23, 174-180.
[12] Hou, Y.Q., Wang, L., Ding, B., Liu, Y., Zhu, H., Liu, J., Li, Y.T., Kang, P., Yin, Y.L. and Wu, G.Y. (2011) Alpha-Ketoglutarate and Intestinal Function. Frontiers in Bioscience (Landmark Ed), 16, 1186-1196.
http://dx.doi.org/10.2741/3783
[13] Tang, D., Kang, R., Zeh III, H.J. and Lotze, M.T. (2011) High-Mobility Group Box 1, Oxidative Stress, and Disease. Antioxidants & Redox Signaling, 14, 1315-1335.
http://dx.doi.org/10.1089/ars.2010.3356
[14] Fuchs, M., Engel, J., Campos, M., Matejec, R., Henrich, M., Harbach, H., et al. (2009) Intracellular Alpha-Keto Acid Quantification by Fluorescence-HPLC. Amino Acids, 36, 1-11.
http://dx.doi.org/10.1007/s00726-008-0033-x
[15] Roth, E. (2008) Nonnutritive Effects of Glutamine. Journal of Nutrition, 138, 2025S-2031S.
[16] Cai, B., Deitch, E.A. and Ulloa, L. (2010) Novel Insights for Systemic Inflammation in Sepsis and Hemorrhage. Mediators of Inflammation, 2010, Article ID: 642462.
[17] Deng, Z.H., Ti, D.D., Xue, H., Lin, J., Wang, L.H. and Yan, G.T. (2009) Effects of Ethyl Pyruvate on Injuries of Sepsis in Mice. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 21, 460-462.
[18] Fink, M.P. (2008) Ethyl Pyruvate. Current Opinion in Anaesthesiology, 21, 160-167.
http://dx.doi.org/10.1097/ACO.0b013e3282f63c2e
[19] Jacobs, C.C., Holcombe, S.J., Cook, V.L., Gandy, J.C., Hauptman, J.G. and Sordillo, L.M. (2013) Ethyl Pyruvate Diminishes the Inflammatory Response to Lipopolysaccharide Infusion in Horses. Equine Veterinary Journal, 45, 333- 339.
http://dx.doi.org/10.1111/j.2042-3306.2012.00634.x
[20] Kung, C.W., Lee, Y.M., Cheng, P.Y., Peng, Y.J. and Yen, M.H. (2011) Ethyl Pyruvate Reduces Acute Lung Injury via Regulation of iNOS and HO-1 Expression in Endotoxemic Rats. Journal of Surgical Research, 167, e323-e331.
http://dx.doi.org/10.1016/j.jss.2011.01.006
[21] Onur, E., Akalin, B., Memisoglu, K., Karip, A.B., Aydin, M.T., Altun, H. and Ekci, B. (2012) Ethyl Pyruvate Improves Healing of Colonic Anastomosis in a Rat Model of Peritonitis. Surgical Innovation, 19, 394-398.
http://dx.doi.org/10.1177/1553350611432158
[22] Zhou, F. (2009) Stable Aqueous Solution Containing Sodium Pyruvate, and the Preparation Thereof. IPC8 Class: AA61K3314FI, USPC Class: 424677.
[23] Mathioudakis, D., Engel, J., Welters, I.D., Dehne, M.G., Matejec, R., Harbach, H., et al. (2011) Pyruvate: Immunonutritional Effects on Neutrophil Intracellular Amino or Alpha-Keto Acid Profiles and Reactive Oxygen Species Production. Amino Acids, 40, 1077-1090.
http://dx.doi.org/10.1007/s00726-010-0731-z
[24] Mühling, J., Fuchs, M., Dehne, M.G., Sablotzki, A., Menges, T., Weber, B. and Hempelmann, G. (1999) Quantitative Determination of Free Intracellular Amino Acids in Single Human Polymorphonuclear Leucocytes: Recent Developments in Sample Preparation and High-Performance Liquid Chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 728, 157-166.
http://dx.doi.org/10.1016/S0378-4347(99)00114-0
[25] Mühling, J., Fuchs, M., Campos, M.E., Gonter, J., Engel, J.M., Sablotzki, A., et al. (2003) Quantitative Determination of Free Intracellular Alpha-Keto Acids in Neutrophils. Journal of Chromatography B, 789, 383-392.
http://dx.doi.org/10.1016/S1570-0232(03)00163-6
[26] Mühling, J., Fuchs, M., Fleck, C., Sablotzki, A., Krüll, M., Dehne, M.G., Gonter, J., Weiss, S., Engel, J. and Hempelmann, G. (2002) Effects of Arginine, L-alanyl-L-glutamine or Taurine on Neutrophil (PMN) Free Amino Acid Profiles and Immune Functions in Vitro. Amino Acids, 22, 39-53.
http://dx.doi.org/10.1007/s726-002-8200-9
[27] Abunnaja, S., Cuviello, A. and Sanchez, J.A. (2013) Enteral and Parenteral Nutrition in the Perioperative Period: State of the Art. Nutrients, 5, 608-623.
http://dx.doi.org/10.3390/nu5020608
[28] Pierre, J.F., Heneghan, A.F., Lawson, C.M., Wischmeyer, P.E., Kozar, R.A. and Kudsk, K.A. (2013) Pharmaconutrition Review, Physiological Mechanisms. JPEN Journal of Parenteral and Enteral Nutrition, 37, 51s-65s.
http://dx.doi.org/10.1177/0148607113493326
[29] Weimann, A. (2013) Immunonutrition in Intensive Care Medicine. Medizinische Klinik, Intensivmedizin und Notfallmedizin, 108, 85-94; Quiz 95.
[30] Gabrilovich, D.I. (1999) The Neutrophils, New Outlook for Old Cells. Imperial College Press, London.
[31] Mühling, J., Fuchs, M., Campos, M., Gonter, J., Sablotzki, A., Engel, J., et al. (2004) Effects of Ornithine on Neutrophil (PMN) Free Amino Acid and Alpha-Keto Acid Profiles and Immune Functions in Vitro. Amino Acids, 27, 313-319.
http://dx.doi.org/10.1007/s00726-004-0126-0
[32] Mates, J.M., Segura, J.A., Martin-Rufian, M., Campos-Sandoval, J.A., Alonso, F.J. and Marquez, J. (2013) Glutaminase Isoenzymes as Key Regulators in Metabolic and Oxidative Stress against Cancer. Current Molecular Medicine, 13, 514-534.
http://dx.doi.org/10.2174/1566524011313040005
[33] Moinard, C., Caldefie, F., Walrand, S., Tridon, A., Chassagne, J., Vasson, M.P. and Cynober, L. (2002) Effects of Ornithine 2-Oxoglutarate on Neutrophils in Stressed Rats: Evidence for the Involvement of Nitric Oxide and Polyamines. Clinical Science, 102, 287-295.
http://dx.doi.org/10.1042/CS20010162
[34] Moinard, C., Caldefie-Chezet, F., Walrand, S., Vasson, M.P. and Cynober, L. (2002) Evidence that Glutamine Modulates Respiratory Burst in Stressed Rat Polymorphonuclear Cells through Its Metabolism into Arginine. British Journal of Nutrition, 88, 689-695.
http://dx.doi.org/10.1079/BJN2002724
[35] Demaria, S., Pikarsky, E., Karin, M., Coussens, L.M., Chen, Y.C., et al. (2010) Cancer and Inflammation, Promise for Biologic Therapy. Journal of Immunotherapy, 33, 335-351.
http://dx.doi.org/10.1097/CJI.0b013e3181d32e74
[36] Sybirna, N., Dziewulska-Szwajkowska, D., Barska, M. and Dzugaj, A. (2006) Mononuclear and Polymorphonuclear Leukocytes Show Increased Fructose-1,6-Bisphosphatase Activity in Patients with Type 1 Diabetes Mellitus. Cell Biology International, 30, 624-630.
http://dx.doi.org/10.1016/j.cellbi.2006.03.008
[37] Castell, L., Vance, C., Abbott, R., Marquez, J. and Eggleton, P. (2004) Granule Localization of Glutaminase in Human Neutrophils and the Consequence of Glutamine Utilization for Neutrophil Activity. Journal of Biological Chemistry, 279, 13305-13310.
http://dx.doi.org/10.1074/jbc.M309520200
[38] Newsholme, P., Curi, R., Pithon Curi, T.C., Murphy, C.J., Garcia, C. and Pires de Melo, M. (1999) Glutamine Metabolism by Lymphocytes, Macrophages, and Neutrophils: Its Importance in Health and Disease. Journal of Nutritional Biochemistry, 10, 316-324.
http://dx.doi.org/10.1016/S0955-2863(99)00022-4
[39] Pithon-Curi, T.C., De Melo, M.P. and Curi, R. (2004) Glucose and Glutamine Utilization by Rat Lymphocytes, Monocytes and Neutrophils in Culture: A Comparative Study. Cell Biochemistry and Function, 22, 321-326.
http://dx.doi.org/10.1002/cbf.1109
[40] Mayadas, T.N., Cullere, X. and Lowell, C.A. (2014) The Multifaceted Functions of Neutrophils. Annual Review of Pathology, 9, 181-218.
http://dx.doi.org/10.1146/annurev-pathol-020712-164023
[41] Wilgus, T.A., Roy, S. and McDaniel, J.C. (2013) Neutrophils and Wound Repair: Positive Actions and Negative Reactions. Advances in Wound Care, 2, 379-388.
http://dx.doi.org/10.1089/wound.2012.0383
[42] Fauth, U., Schlechtriemen, T., Heinrichs, W., Puente-Gonzalez, I. and Halmagyi, M. (1993) The Measurement of Enzyme Activities in the Resting Human Polymorphonuclear Leukocyte-Critical Estimate of a Method. European Journal of Clinical Chemistry and Clinical Biochemistry, 31, 5-16.
[43] Fauth, U., Heinrichs, W., Puente-Gonzalez, I. and Halmagyi, M. (1990) Maximal Turnover Rates of Glycolysis Enzymes and of the Citrate Cycle of Separated Granulocytes in the Postoperative Period. Infusionstherapie, 17, 178-183.
[44] Jemelin, M. and Frei, J. (1970) Leukocyte Energy Metabolism. 3. Anaerobic and Aerobic ATP Production and Related Enzymes. Enzymologia Biologica et Clinica (Basel), 11, 298-323.
[45] Gabrilovich, D. (2013) The Neutrophils. New Outlook for Old Cells. 3rd Edition, Imperial College Press, London.
http://dx.doi.org/10.1142/p823
[46] Break, T.J., Jun, S., Indramohan, M., Carr, K.D., Sieve, A.N., Dory, L. and Berg, R.E. (2012) Extracellular Superoxide Dismutase Inhibits Innate Immune Responses and Clearance of an Intracellular Bacterial Infection. Journal of Immunology, 188, 3342-3350.
http://dx.doi.org/10.4049/jimmunol.1102341
[47] Radi, R. (2013) Peroxynitrite, a Stealthy Biological Oxidant. Journal of Biological Chemistry, 288, 26464-26472.
http://dx.doi.org/10.1074/jbc.R113.472936
[48] Vitecek, J., Lojek, A., Valacchi, G. and Kubala, L. (2012) Arginine-Based Inhibitors of Nitric Oxide Synthase: Therapeutic Potential and Challenges. Mediators of Inflammation, 2012, Article ID: 318087.
[49] Wu, G., Bazer, F.W., Davis, T.A., Kim, S.W., Li, P., Marc Rhoads, J., et al. (2009) Arginine Metabolism and Nutrition in Growth, Health and Disease. Amino Acids, 37, 153-168.
http://dx.doi.org/10.1007/s00726-008-0210-y
[50] Wu, G.Y. (2009) Amino Acids: Metabolism, Functions, and Nutrition. Amino Acids, 37, 1-17.
http://dx.doi.org/10.1007/s00726-009-0269-0
[51] Buijs, N., Luttikhold, J., Houdijk, A.P. and van Leeuwen, P.A. (2012) The Role of a Disturbed Arginine/NO Metabolism in the Onset of Cancer Cachexia: A Working Hypothesis. Current Medicinal Chemistry, 19, 5278-5286.
http://dx.doi.org/10.2174/092986712803833290
[52] Munder, M. (2009) Arginase: An Emerging Key Player in the Mammalian Immune System. British Journal of Pharmacology, 158, 638-651.
http://dx.doi.org/10.1111/j.1476-5381.2009.00291.x
[53] Keough, M.P., Hayes, C.S., DeFeo, K. and Gilmour, S.K. (2011) Elevated Epidermal Ornithine Decarboxylase Activity Suppresses Contact Hypersensitivity. Journal of Investigative Dermatology, 131, 158-166.
http://dx.doi.org/10.1038/jid.2010.263
[54] Lavoie-Lamoureux, A., Martin, J.G. and Lavoie, J.P. (2014) Characterization of Arginase Expression by Equine Neutrophils. Veterinary Immunology and Immunopathology, 157, 206-213.
http://dx.doi.org/10.1016/j.vetimm.2013.12.007
[55] Cervelli, M., Amendola, R., Polticelli, F. and Mariottini, P. (2012) Spermine Oxidase: Ten Years after. Amino Acids, 42, 441-450.
http://dx.doi.org/10.1007/s00726-011-1014-z
[56] Brooks, W.H. (2012) Autoimmune Diseases and Polyamines. Clinical Reviews in Allergy & Immunology, 42, 58-70.
http://dx.doi.org/10.1007/s12016-011-8290-y
[57] Minois, N., Carmona-Gutierrez, D. and Madeo, F. (2011) Polyamines in Aging and Disease. Aging (Albany NY), 3, 716-732.
[58] Wallace, H.M. (2009) The Polyamines: Past, Present and Future. Essays in Biochemistry, 46, 1-10.
http://dx.doi.org/10.1042/bse0460001
[59] Casero, R.A. and Pegg, A.E. (2009) Polyamine Catabolism and Disease. Biochemical Journal, 421, 323-338.
http://dx.doi.org/10.1042/BJ20090598
[60] Fortin, C.F., McDonald, P.P., Fulop, T. and Lesur, O. (2010) Sepsis, Leukocytes, and Nitric Oxide (NO): An Intricate Affair. Shock, 33, 344-352.
http://dx.doi.org/10.1097/SHK.0b013e3181c0f068
[61] Valenca, S.S., Rueff-Barroso, C.R., Pimenta, W.A., Melo, A.C., Nesi, R.T., et al. (2011) L-NAME and L-Arginine Differentially Ameliorate Cigarette Smoke-Induced Emphysema in Mice. Pulmonary Pharmacology & Therapeutics, 24, 587-594.
http://dx.doi.org/10.1016/j.pupt.2011.05.006
[62] Weaver, H., Shukla, N., Ellinsworth, D. and Jeremy, J.Y. (2012) Oxidative Stress and Vein Graft Failure: A Focus on NADH Oxidase, Nitric Oxide and Eicosanoids. Current Opinion in Pharmacology, 12, 160-165.
http://dx.doi.org/10.1016/j.coph.2012.01.005
[63] Singh, S. and Gupta, A.K. (2011) Nitric Oxide: Role in Tumour Biology and iNOS/NO-Based Anticancer Therapies. Cancer Chemotherapy and Pharmacology, 67, 1211-1224.
http://dx.doi.org/10.1007/s00280-011-1654-4
[64] Azadniv, M., Torres, A., Boscia, J., Speers, D.M., Frasier, L.M., Utell, M.J. and Frampton, M.W. (2001) Neutrophils in Lung Inflammation: Which Reactive Oxygen Species Are Being Measured? Inhalation Toxicology, 13, 485-495.
http://dx.doi.org/10.1080/08958370151131855
[65] Mühling, J., Engel, J., Halabi, M., Müller, M., Fuchs, M., et al. (2006) Nitric Oxide and Polyamine Pathway-Dependent Modulation of Neutrophil Free Amino-and Alpha-Keto Acid Profiles or Host Defense Capability. Amino Acids, 31, 11-26.
http://dx.doi.org/10.1007/s00726-006-0273-6
[66] Engel, J.M., Mühling, J., Weiss, S., Karcher, B., Lohr, T., Menges, T., Little, S. and Hempelmann, G. (2006) Relationship of Taurine and Other Amino Acids in Plasma and in Neutrophils of Septic Trauma Patients. Amino Acids, 30, 87-94.
http://dx.doi.org/10.1007/s00726-005-0238-1
[67] Hansen, S.H. and Grunnet, N. (2013) Taurine, Glutathione and Bioenergetics. Advances in Experimental Medicine and Biology, 776, 3-12.
http://dx.doi.org/10.1007/978-1-4614-6093-0_1
[68] Buijs, N., Worner, E.A., Brinkmann, S.J., Luttikhold, J., van der Meij, B.S., Houdijk, A.P.J. and van Leeuwen, P.A.M. (2013) Novel Nutritional Substrates in Surgery. Proceedings of the Nutrition Society, 72, 277-287.
http://dx.doi.org/10.1017/S0029665112003047
[69] Ripps, H. and Shen, W. (2012) Review: Taurine: A “Very Essential” Amino Acid. Molecular Vision, 18, 2673-2686.
[70] Fink, M.P. (2007) Ethyl Pyruvate: A Novel Anti-Inflammatory Agent. Journal of Internal Medicine, 261, 349-362.
http://dx.doi.org/10.1111/j.1365-2796.2007.01789.x
[71] Fink, M.P. (2007) Ethyl Pyruvate: A Novel Treatment for Sepsis. Current Drug Targets, 8, 515-518.
http://dx.doi.org/10.2174/138945007780362791
[72] Fink, M.P. (2004) Ethyl Pyruvate: A Novel Treatment for Sepsis and Shock. Minerva Anestesiologica, 70, 365-371.
[73] Reade, M.C. and Fink, M.P. (2005) Bench-to-Bedside Review: Amelioration of Acute Renal Impairment Using Ethyl Pyruvate. Critical Care, 9, 556-560.
http://dx.doi.org/10.1186/cc3892
[74] Mackenzie, I. and Lever, A. (2007) Management of Sepsis. British Medical Journal, 335, 929-932.
http://dx.doi.org/10.1136/bmj.39346.696620.AE
[75] Kao, K.K. and Fink, M.P. (2010) The Biochemical Basis for the Anti-Inflammatory and Cytoprotective Actions of Ethyl Pyruvate and Related Compounds. Biochemical Pharmacology, 80, 151-159.
http://dx.doi.org/10.1016/j.bcp.2010.03.007
[76] Das, U.N. (2006) Pyruvate Is an Endogenous Anti-Inflammatory and Anti-Oxidant Molecule. Medical Science Monitor, 12, RA79-RA84.
[77] Das, U.N. (2006) Is Pyruvate an Endogenous Anti-Inflammatory Molecule? Nutrition, 22, 965-972.
http://dx.doi.org/10.1016/j.nut.2006.05.009
[78] Bates, C.M. and Lin, F. (2005) Future Strategies in the Treatment of Acute Renal Failure: Growth Factors, Stem Cells, and Other Novel Therapies. Current Opinion in Pediatrics, 17, 215-220.
http://dx.doi.org/10.1097/01.mop.0000156269.48510.4e
[79] Aneja, R. and Fink, M.P. (2007) Promising Therapeutic Agents for Sepsis. Trends in Microbiology, 15, 31-37.
http://dx.doi.org/10.1016/j.tim.2006.11.005
[80] Bossola, M., Pacelli, F., Rosa, F., Tortorelli, A. and Doglietto, G.B. (2011) Does Nutrition Support Stimulate Tumor Growth in Humans? Nutrition in Clinical Practice, 26, 174-180.
http://dx.doi.org/10.1177/0884533611399771
[81] Nemeth, T. and Mocsai, A. (2012) The Role of Neutrophils in Autoimmune Diseases. Immunology Letters, 143, 9-19.
http://dx.doi.org/10.1016/j.imlet.2012.01.013
[82] Williams, A.E. and Chambers, R.C. (2014) The Mercurial Nature of Neutrophils: Still an Enigma in ARDS? American Journal of Physiology-Lung Cellular and Molecular Physiology, 306, L217-L230.
http://dx.doi.org/10.1152/ajplung.00311.2013

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