The crucial role of L-arginine in macrophage activation: What you need to know about it

Life Sciences

Volumn 137, Issue , 2015, Pages 44-48

  Pekarova, Michaela ^a   Lojek, Antonin ^a  

^a INSTITUTE OF BIOPHYSICS   (Czech Republic)

Author keywords

G protein coupled receptor; Inflammation; L Arginine; Lipopolysaccharide; Macrophages; Signaling pathways

Indexed keywords

ARGININE; G PROTEIN COUPLED RECEPTOR; NITRIC OXIDE; NITRIC OXIDE SYNTHASE;

BIOAVAILABILITY; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; INTRACELLULAR SIGNALING; MACROPHAGE; MACROPHAGE ACTIVATION; NONHUMAN; REVIEW; ANIMAL; BIOLOGICAL MODEL; BIOSYNTHESIS; IMMUNOLOGY; METABOLISM; SIGNAL TRANSDUCTION;

ANIMALS; ARGININE; BIOLOGICAL AVAILABILITY; HOMEOSTASIS; HUMANS; MACROPHAGE ACTIVATION; MACROPHAGES; MODELS, IMMUNOLOGICAL; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84938365904     PISSN: 00243205     EISSN: 18790631     Source Type: Journal    
DOI: 10.1016/j.lfs.2015.07.012     Document Type: Review

References (90)

1. S. Akashi, R. Shimazu, H. Ogata, Y. Nagai, K. Takeda, M. Kimoto, and K. Miyake Cutting edge: cell surface expression and lipopolysaccharide signaling via the toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages J. Immunol. 164 2000 3471 3475 10.4049/jimmunol.164.7.3471
2. J.P. Andrew, and B. Mayer Enzymatic function of nitric oxide synthases Cardiovasc. Res. 43 1999 521 531 10.1016/S0008-6363(99)00115-7
3. A. Barilli, B.M. Rotoli, R. Visigalli, O. Bussolati, G.C. Gazzola, and V. Dall'Asta Arginine transport in human monocytic leukemia THP-1 cells during macrophage differentiation J. Leukoc. Biol. 90 2011 293 303 10.1189/jlb.0910510
4. H. Betz, J. Kuhse, V. Schmieden, B. Laube, J. Kirsch, and R.J. Harvey Structure and functions of inhibitory and excitatory glycine receptors Ann. N. Y. Acad. Sci. 868 1999 667 676 10.1111/j.1749-6632.1999.tb11343.x
5. R.H. Boger Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide sythase, explains the "L-arginine paradox" and act as a novel cardiovascular risk factor J Nutr 134 2004 2842S 2847S
6. R.G. Bogle, A.R. Baydoun, J.D. Pearson, S. Moncada, and G.E. Mann L-Arginine transport is increased in macrophages generating nitric oxide Biochem. J. 284 1992 15 18
7. S. Bonhomme, L. Belabed, M.C. Blanc, N. Neveux, L. Cynober, and S. Darquy Arginine-supplemented enteral nutrition in critically ill diabetic and obese rats: a dose-ranging study evaluating nutritional status and macrophage function Nutrition 29 2013 305 312 10.1016/j.nut.2012.07.005
8. L. Bosca, M. Zeini, P.G. Traves, and S. Hortelano Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate Toxicology 208 2005 249 258 10.1016/j.tox.2004.11.035
9. S.C. Brennan, T.S. Davies, M. Schepelmann, and D. Riccardi Emerging roles of the extracellular calcium-sensing receptor in nutrient sensing: control of taste modulation and intestinal hormone secretion Br J Nutr 111 Suppl 1 2014 S16 S22
10. C. Breuillard, L. Belabed, S. Bonhomme, M.C. Blanc-Quintin, N. Neveux, R. Couderc, J.P. De Bandt, L. Cynober, and S. Darquy Arginine availability modulates arginine metabolism and TNFα production in peritoneal macrophages from Zucker Diabetic Fatty rats Clin. Nutr. 31 2012 415 421 10.1016/j.clnu.2011.11.012
11. C. Breuillard, S. Bonhomme, R. Couderc, L. Cynober, and J.P. De Bandt In vitro anti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats Br J Nutr 13 2014 1 5 (Epub ahead of print)
12. S. Broer Adaptation of plasma membrane amino acid transport mechanisms to physiological demands Pflugers Arch. 444 2002 457 466 10.1007/s00424-002-0840-y
13. V. Bronte, and P. Zanovello Regulation of immune responses by L-arginine metabolism Immunology 5 2005 641 654 10.1038/nri1668
14. J. Bryk, J.B. Ochoa, M.I. Correia, V. Munera-Seeley, and P.J. Popovic Effect of citrulline and glutamine on nitric oxide production in RAW 264.7 cells in an arginine-depleted environment JPEN J. Parenter. Enteral Nutr. 32 2008 377 383 10.1177/0148607108319807
15. A. Castrillo, D.J. Pennington, F. Otto, P.J. Parker, M.J. Owen, and L. Bosca Protein kinase Cepsilon is required for macrophage activation and defense against bacterial infection J Exp Med 194 2001 1231 1242 10.1084/jem.194.9.1231
16. M. Cathcart Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages. Contribution to atherosclerosis Atherioscler Thromb Vasc Biol 24 2004 23 28 10.1161/01.ATV.0000097769.47306.12
17. Y.H. Chen, C.H. Lee, L.S. Hsu, C.C. Hsiao, and H.C. Lo Appropriate dose of parenteral arginine enhances immunity of peripheral blood cells and splenocytes in rats with subacute peritonitis JPEN J. Parenter. Enteral Nutr. 36 2012 741 749 10.1177/0148607111429793
18. B. Christiansen, K.B. Hansen, P. Wellendorph, and H. Brauner-Osborne Pharmacological characterization of mouse GPRC6A, an L-α-amino-acid receptor modulated by divalent cations Brit J Pharmacol 150 2007 798 807 10.1038/sj.bjp.0707121
19. J. Cohen The immunopathogenesis of sepsis Nature 420 2002 885 891 10.1038/nature01326
20. A.D. Conigrave, A.H. Francs, E.M. Brown, and S.J. Quinn l-Amino acid sensing by the calcium-sensing receptor: a general mechanism for youpling protein and calcium metabolism? Eur. J. Clin. Nutr. 56 2002 1072 1080 10.1038/sj.ejcn.1601463
21. A.D. Conigrave, S.J. Quinn, and E.M. Brown l-Amino acid sensing by the extracellular Ca2 +-sensing receptor Proc. Natl. Acad. Sci. U. S. A. 97 2000 4814 4819 10.1073/pnas.97.9.4814
22. P. Das, A. Lahiri, A. Lahiri, M. Sen, N. Iyer, N. Kapoor, K.N. Balaji, and D. Chakravortty Cationic amino acid transporters and Salmonella Typhimurium ArgT collectively regulate arginine availability towards intracellular Salmonella growth PLoS One 5 2010 e15466 10.1371/journal.pone.0015466
23. I.B. Debats, T.G. Wolfs, T. Gotoh, J.P. Cleutjens, C.J. Peutz-Kootstra, and R.R. van der Hulst Role of arginine in superficial wound healing in man Nitric Oxide 21 2009 175 183 10.1016/j.niox.2009.07.006
24. S. El-Gayar, H. Thuring-Nahler, J. Pfeilschifter, M. Rollinghoff, and C. Bogdan Translational control of inducible nitric oxide synthase by IL-13 and arginine availability in inflammatory macrophages J. Immunol. 171 2003 4561 4568 10.4049/jimmunol.171.9.4561
25. J. Fernandez, A.B. Lopez, C. Wang, R. Mishra, L. Zhou, I. Yaman, M.D. Snider, and M. Hatzoglou Transcriptional control of the arginine/lysine transporter, cat-1, by physiological stress J. Biolumin. Chemilumin. 278 2003 50000 50009 10.1074/jbc.M305903200
26. A. Geelhaar-Karsch, K. Schinnerling, K. Conrad, J. Friebel, K. Allers, T. Schneider, and V. Moos Evaluation of arginine metabolism for the analysis of M1/M2 macrophage activation in human clinical specimens Inflamm. Res. 62 2013 865 869 10.1007/s00011-013-0642-z
27. R. Gill, A. Tsung, and T. Billiar Linking oxidative stress to inflammation: Toll-like receptors Free Radic. Biol. Med. 48 2010 1121 1132 10.1016/j.freeradbiomed.2010.01.006
28. B. Grallert, and E. Boye The Gcn2 kinase as a cell cycle regulator Cell Cycle 22 2007 2768 2772 10.4161/cc.6.22.4933
29. M. Guha, and N. Mackman LPS induction of gene expression in human monocytes Cell. Signal. 13 2001 85 94 10.1016/S0898-6568(00)00149-2
30. H.P. Harding, Y. Zhang, H. Zeng, I. Novoa, P.D. Lu, M. Calfon, N. Sadri, C. Yun, B. Popko, R. Paules, D.F. Stojdl, J.C. Bell, T. Hettmann, J.M. Leiden, and D. Ron An integrated stress response regulated amino acid metabolism and resistance to oxidative stress Mol. Cell 11 2003 619 633 10.1016/S1097-2765(03)00105-9
31. M. Hatziapostolou, G. Koukos, C. Polytarchou, F. Kottakis, O. Serebrennikova, A. Kuliopulos, and P.N. Tsichlis Tumor progression locus 2 regulates signal-induced calcium release from the endoplamic reticulum and cell migration Sci. Signal. 4 ra55 2011 10.1126/scisignal.2002006
32. S. Hortelano, M. Zeini, and L. Bosca Nitric oxide and resolution of inflammation Methods Enzymol. 359 2002 459 465 10.1016/S0076-6879(02)59208-9
33. R. Hyde, P.M. Taylor, and H.S. Hundal Amino acid transporters: roles in amino acid sensing and signaling in animal cells Biochem. J. 373 2003 1 18 10.1042/BJ20030405
34. H. Iwase, H. Kariyazono, J. Arima, H. Yamamoto, and K. Nakamura Nutritional effect of oral supplement enriched in ω - 3 fatty acids, arginine, RNA on immune response and leukocyte-platelet aggregate formation in patients undergoing cardiac surgery Nutr Metab Insights 7 2014 39 46 10.4137/NMI.S13810
35. M.S. Joshi, B. Ferguson, F.K. Johnson, R.A. Johnson, S. Parthasarathy, and J.R. Lancaster Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells PNAS 104 2007 9982 9987 10.1073/pnas.0506824104
36. C. Jousse, J. Averous, A. Bruhat, V. Carraro, S. Mordier, and P. Fafournoux Amino acids as resulators of gene expression: molecular mechanisms Biochem. Biophys. Res. Commun. 313 2004 447 452 10.1016/j.bbrc.2003.07.020
37. G. Kagemann, H. Sies, and O. Schnorr Limited availability of L-arginine increases DNA-binding activity of NF-kappaB and contributes to regulation of iNOS expression J. Mol. Med. 85 2007 723 732 10.1007/s00109-007-0168-3
38. K. Kapp, S. Prüfer, C.S. Michel, A. Habermeier, C. Luckner-Minden, T. Giese, J. Bomalaski, C.D. Langhans, P. Kropf, I. Müller, E.I. Closs, M.P. Radsak, and M. Munder Granulocyte functions are independent of arginine availability J. Leukoc. Biol. 96 2014 1047 1053 10.1189/jlb.3AB0214-082R
39. S.J. Kirk, M. Hurson, M.C. Regan, D.R. Holt, H.L. Wasserkrug, and A. Barbul Arginine stimulates wound healing and immune function in elderly human beings Surgery 114 1993 155 159
40. T. Konig, C. Bogdan, and U. Schleicher Translational repression of inducible NO synthase in macrophages by L-arginine depletion is not associated with an increased phosphorylation of eF2α Immunobiology 214 2009 822 827 10.1016/j.imbio.2009.06.008
41. B. Lamas, J. Vergnaud-Gauduchon, N. Goncalves-Mendes, O. Perche, A. Rossary, M.P. Vasson, and M.C. Farges Altered functions of natural killer cells in response to L-Arginine availability Cell. Immunol. 280 2012 182 190 10.1016/j.cellimm.2012.11.018
42. D.L. Laskin, V.R. Sunil, L. Fakhrzadeh, A. Groves, A.J. Gow, and J.D. Laskin Macrophages, reactive nitrogen species, and lung injury Ann. N. Y. Acad. Sci. 1203 2010 60 65 10.1111/j.1749-6632.2010.05607.x
43. J. Lee, H. Ryu, R.J. Ferrante, S.M. Morris, and R.R. Ratan Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox Proc. Natl. Acad. Sci. U. S. A. 100 2003 4843 4848 10.1073/pnas.0735876100
44. H. Maarsingh, J. Zaagsma, and H. Meurs Arginine homeostasis in allergic asthma Eur. J. Pharmacol. 585 2008 375 384 10.1016/j.ejphar.2008.02.096
45. C.L. MacLeod, K.D. Finley, and D.K. Kakuda y +-type cationic amino acid transport: expression and regulation of the mCAT genes J Exp Biol 196 1994 109 121
46. J. MacMicking, Q.W. Xie, and C. Nathan Nitric oxide and macrophage function Annu. Rev. Immunol. 15 1997 323 350 10.1146/annurev.immunol.15.1.323
47. F.L. MacRae, and S. Fazio Macrophages, inflammation, and atherosclerosis Int. J. Obes. 27 2003 S35 S40 10.1038/sj.ijo.0802498
48. P. Martin-Sanz, S. Hortelano, N.A. Callejas, N. Goren, M. Casado, M. Zeini, and L. Bosca Nitric oxide in liver inflammation and regeneration Metab. Brain Dis. 17 2002 325 334 10.1023/A:1021909902310
49. J.C. Matthews, and K.J. Anderson Recent advances in amino acid transporters and excitatory amino acid receptors Curr Opin Clin Nutr Metab Care 5 2002 77 84 10.1097/00075197-200201000-00014
50. B. Mayer, and B. Hemmens Biosynthesis and action of nitric oxide in mammalian cells Trends Biochem. Sci. 22 1997 477 481 10.1016/S0968-0004(97)01147-X
51. V. Mieulet, L. Yan, C. Choisy, K. Sully, J. Procter, A. Kouroumalis, S. Krywawych, M. Pende, S.C. Ley, C. Mainard, and R.F. Lamb TPL-2-mediated activation of MAPK downstream of TLR4 signaling is coupled to arginine availability Sci. Signal. 3 ra61 2010 10.1126/scisignal.2000934
52. C.R. Morris New strategies for the treatment of pulmonary hypertension in sickle cell disease: the rationale for arginine therapy Treat Respir Med 5 2006 31 45 10.2165/00151829-200605010-00003
53. C.R. Morris, M. Poljakovic, L. Lavrisha, L. Machado, F.A. Kuypers, and S.M. Morris Decreased arginine bioavailability and increased serum arginase activity in asthma Am. J. Respir. Crit. Care Med. 170 2004 148 153 10.1164/rccm.200309-1304OC
54. S.M. Morris Arginine metabolism boundaries of our knowledge J Nutr 137 2007 1602S 1609S
55. S.M. Morris Jr. Arginases and arginine deficiency syndromes Curr Opin Clin Nutr Metab Care 15 2012 64 70 10.1097/MCO.0b013e32834d1a08
56. S.M. Morris, D. Kepka-Lenhart, and L. Chen Differential regulation of arginases and inducible nitric oxide synthase in murine macrophage cells Am. J. Phys. 275 1998 E740 E747
57. M. Munder, M. Engelhardt, D. Knies, S. Medenhoff, G. Wabnitz, C. Luckner-Minden, N. Feldmeyer, R.H. Voss, P. Kropf, I. Müller, R. Conradi, Y. Samstag, M. Theobald, A.D. Ho, H. Goldschmidt, and M. Hundemer Cytotoxicity of tumor antigen specific human T cells is unimpaired by arginine depletion PLoS One 8 2013 e63521 10.1371/journal.pone.0063521
58. G. Nelson, J. Chandrashekar, M.A. Hoon, L. Feng, G. Zhao, N.J. Ryba, and C.S. Zuker An amino-acid taste receptor Nature 416 2002 199 202 10.1038/nature726
59. B. Nicholson, C.K. Manner, J. Kleeman, and C.L. MacLeod Sustained nitric oxide produciton in macrophages requires the arginine transporter CAT2∗ J. Biolumin. Chemilumin. 276 2001 15881 15885 10.1074/jbc.M010030200
60. K.A. Niese, M.G. Chiaramonte, L.G. Ellies, M.E. Rothenberg, and N. Zimmermann The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis Respir. Res. 11 87 2010 10.1186/1465-9921-11-87
61. L.A. O'Neill How Toll-like receptors signal: what we know and what we don't know Curr. Opin. Immunol. 18 2006 3 9 10.1016/j.coi.2005.11.012
62. L.A. O'Neill, D. Golenbock, and A.G. Bowie The history of Toll-like receptors - redefining innate immunity Nat. Rev. Immunol. 13 2013 453 460 10.1038/nri3446
63. M. Pekarova, J. Kralova, L. Kubala, M. Ciz, A. Lojek, C. Gregor, and J. Hrbac Continuous electrochemical monitoring of nitric oxide production in murine macrophage cell line RAW 264.7 Anal. Bioanal. Chem. 394 2009 1497 1504 10.1007/s00216-009-2813-x
64. M. Pekarova, L. Kubala, M. Martiskova, L. Bino, M. Twarogova, A. Klinke, T.K. Rudolph, Z. Kuchtova, H. Kolarova, G. Ambrozova, R. Kuchta, J. Kadlec, and A. Lojek Asymmetric dimethylarginine regulates the lipopolysaccharide-induced nitric oxide production in macrophages by suppressing the activation of NF-kappaB and iNOS expression Eur. J. Pharmacol. 713 2013 68 77 10.1016/j.ejphar.2013.05.001
65. M. Pekarova, L. Kubala, H. Martiskova, I. Papezikova, S. Kralova, S. Baldus, A. Klinke, R. Kuchta, J. Kadlec, Z. Kuchtova, H. Kolarova, and A. Lojek The unique role of dietary L-arginine in the acceleration of peritoneal macrophage sensitivity to bacterial endotoxin Immunol. Res. 56 2013 73 84 10.1007/s12026-012-8379-2
66. M. Pekarova, A. Lojek, H. Martiskova, O. Vasicek, L. Bino, A. Klinke, D. Lau, R. Kuchta, J. Kadlec, R. Vrba, and L. Kubala New role for L-arginine in regulation of inducible nitric-oxide-synthase-derived superoxide anion production in raw 264.7 macrophages ScientificWorldJournal 11 2011 2443 2457 10.1100/2011/321979
67. E. Peranzoni, I. Marigo, L. Dolcetti, S. Ugel, N. Sonda, E. Taschin, B. Mantelli, V. Bronte, and P. Zanovello Role of arginine metabolism in immunity and immunopathology Immunobiology 212 2008 795 812 10.1016/j.imbio.2007.09.008
68. P. Raber, A.C. Ochoa, and P.C. Rodríguez Metabolism of L-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives Immunol. Investig. 41 2012 614 634 10.3109/08820139.2012.680634
69. M. Rath, I. Müller, P. Kropf, E.I. Closs, and M. Munder Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages Front. Immunol. 5 2014 532 10.3389/fimmu.2014.00532
70. W. Ren, S. Chen, J. Yin, J. Duan, T. Li, G. Liu, Z. Feng, B. Tan, Y. Yin, and G. Wu Dietary arginine supplementation of mice alters the microbial population and activates intestinal innate immunity J Nutr 144 2014 988 995 10.3945/jn.114.192120
71. J.E. Qualls, G. Neale, A.M. Smith, M.S. Koo, A.A. DeFreitas, H. Zhang, G. Kaplan, S.S. Watowich, and P.J. Murray Arginine usage in mycobacteria-infected macrophages depends on autocrine-paracrine cytokine signaling Sci. Signal. 3 ra62 2010 10.1126/scisignal.2000955
72. I.E. Quirino, M.B. Carneiro, V.N. Cardoso, R. das Graças Carvalho Dos Santos, L.Q. Vieira, J.A. Fiuza, J.I. Alvarez-Leite, S. de Vasconcelosgeneroso, and M.I. Correia Arginine supplementation induces arginase activity and inhibits TNF-α synthesis in mice spleen macrophages after intestinal obstruction JPEN J. Parenter. Enteral Nutr. 2014 (pii: 0148607114546374. [Epub ahead of print])
73. S. Saito, and M. Tominaga Functional diversity and evolutionary dynamics of thermoTRP channels Cell Calcium 57 2015 214 221 10.1016/j.ceca.2014.12.001
74. A.K. Sikalidis Amino acids and immune response: a role for cysteine, glutamine, phenylalanine, tryptophan and arginine in T-cell function and cancer? Pathol. Oncol. Res. 21 2015 9 17 10.1007/s12253-014-9860-0
75. O. Schnorr, M. Schuier, G. Kagemann, R. Wolf, M. Walz, T. Ruzicka, E. Mayatepek, M. Laryea, C.V. Suschek, V. Kolb-Bachofen, and H. Sies Arginase-1 overexpression induces cationic amino acid transporter in psoriasis Free Radic. Biol. Med. 38 2005 1073 1079 10.1016/j.freeradbiomed.2005.01.005
76. J.L. Swantek, M.H. Cobb, and T.D. Geppert Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK Mol. Cell. Biol. 17 1997 6274 6282
77. M.J. Sweet, and D.A. Hume Endotoxin signal transduction in macrophages J. Leukoc. Biol. 60 1996 8 26
78. M. Wehling-Henricks, M.C. Jordan, T. Gotoh, W.W. Grody, K.P. Roos, and J.G. Tidball Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy PLoS One 5 2010 e10763 10.1371/journal.pone.0010763
79. F. Wittmann, N. Prix, S. Mayr, P. Angele, M.W. Wichmann, N.K. van den Engel, T. Hernandez-Richter, I.H. Chaudry, K.W. Jauch, and M.K. Angele L-Arginine improves wound healing after trauma-hemorrhage by increasing collagen synthesis J Trauma 59 2005 162 168 10.1097/01.TA.0000171529.06625.A8
80. G. Wu, and J.T. Brosnan Macrophages can convert citrulline into arginine Biochem. J. 281 1992 45 48
81. G. Wu, and S.M. Morris Arginine metabolism: nitric oxide and beyond Biochem. J. 336 1998 1 17
82. H. Xu, Y. Feng, G. Chen, X. Zhu, W. Pang, Y. Du, Q. Wang, Z. Qi, and Y. Cao L-Arginine exacerbates experimental cerebral malaria by enhancing pro-inflammatory responses Tohoku J. Exp. Med. 236 2015 21 31 10.1620/tjem.236.21
83. L. Yan, and R.F. Lamb Signalling by amino acid nutrients Biochem. Soc. Trans. 39 2011 443 445 10.1042/BST0390443
84. X. Yang, J.Y.C. Ma, M.W. Barger, and J.K.H. Ma Transport and utilization of arginine and arginine-containing peptides by rat alveolar macrophages Pharm. Res. 19 2002 825 831 10.1023/A:1016132200104
85. Z. Yang, and X.F. Ming Functions of arginase isoforms in macrophage inflammatory responses: impact on cardiovascular diseases and metabolic disorders Front. Immunol. 5 2014 533 10.3389/fimmu.2014.00533
86. A. Yeramian, L. Martin, L. Arpa, J. Bertran, C. Soler, C. McLeod, M. Modolell, M. Palacin, J. Lloberas, and A. Celada Macrophages require distinct arginine catabolism and transport system for proliferation and for activation Eur. J. Immunol. 26 2006 1516 1526 10.1002/eji.200535694
87. H.R. Yu, H.C. Kuo, L.T. Huang, C.C. Chen, Y.L. Tain, J.M. Sheen, M.M. Tiao, H.C. Huang, K.D. Yang, C.Y. Ou, and T.Y. Hsu L-Arginine modulates neonatal lymphocyte proliferation through an interleukin-2 independent pathway Immunology 143 2014 184 192 10.1111/imm.12300
88. X. Zhu, Y. Pan, Y. Li, L. Cui, and Y. Cao Supplement of L-Arg improves protective immunity during early-stage Plasmodium yoelii 17XL infection Parasite Immunol. 34 2012 412 420 10.1111/j.1365-3024.2012.01374.x
89. N. Feldmeyer, G. Wabnitz, S. Leicht, C. Luckner-Minden, M. Schiller, T. Franz, R. Conradi, P. Kropf, I. Müller, A.D. Ho, Y. Samstag, and M. Munder Arginine deficiency leads to impaired cofilin dephosphorylation in activated human T lymphocytes Int. Immunol. 24 5 2012 303 313 10.1093/intimm/dxs004
90. A. Yeramian, L. Martin, L. Arpa, J. Bertran, C. Soler, C. McLeod, M. Modolell, M. Palacín, J. Lloberas, and A. Celada Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur. J. Immunol. 36 6 2006 1516 1526