Signal Transduction Changes in Human Neutrophils with Age

  • Carl FortinEmail author
  • Tamas Fulop
  • Anis Larbi
  • Gilles Dupuis
Living reference work entry


The role of innate immune cells as first line of defense against pathogens and foreign invasion has been widely recognized. Among the innate immune cells, neutrophils represent the most potent phagocytic cell and possess an elaborate arsenal capable of efficiently neutralizing pathogens; in addition, neutrophils modulate adaptive immunity by secreting cytokines. Over the years, it has become clear that human aging negatively affects neutrophils’ responses. A common alteration underlying these functional changes in aging is the decrease of phosphorylated forms of signaling molecules after receptor engagement. The consequences of aging on human neutrophils may impair the activation of immune responses and contribute to poorer vaccine responses and greater morbidity and mortality from infectious diseases in older adults. This chapter describes our current knowledge of the age-related alterations in receptors for the Nformyl-met-leu-phe (fMLP) peptide, for the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), and for Toll-like receptors (TLR) and triggering receptor expressed on myeloid cells-1 (TREM-1).


Aging Human neutrophils Signal transduction N-formyl-met-leu-phe peptide receptor GM-CSF receptor TREM-1 receptor Lipid rafts 



We apologize to members of the scientific community whose contributions could not be cited. This work was supported by a grant-in-aid from the National Science and Engineering Research Council of Canada (No 249549), Research Center on Aging of Sherbrooke, the ImAginE Consortium, and the Canadian Institute of Health Research (No 63149).


  1. Alemán OR, Mora N, Cortes-Vieyra R, Uribe-Querol E, Rosales C (2016) Differential use of human neutrophil Fcγ receptors for inducing neutrophil extracellular trap formation. J Immunol Res 2016:2908034PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alvarez E, Ruiz-Guttierrez V, Sobrino F, Santa-María C (2001) Age-related changes in membrane lipid composition, fluidity and respiratory burst in rat peripheral neutrophils. Clin Exp Immunol 124(1):95–102PubMedPubMedCentralCrossRefGoogle Scholar
  3. Altznauer F, Martinelli S, Yousefi S, Thürig C, Schmid I, Conway EM, Schöni MH, Vogt P, Mueller C, Fey MF, Zangemeister-Wittke U, Simon HU (2004) Inflammation-associated cell cycle-independent block of apoptosis by survivin in terminally differentiated neutrophils. J Exp Med 199(10):1343–54Google Scholar
  4. Arts RJ, Joosten LA, van der Meer JW, Netea MG (2013) TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol 93(2):209–215PubMedCrossRefGoogle Scholar
  5. Balasubramanian N, Advani SH, Zingde SM (2002) Protein kinase C isoforms in normal and leukemic neutrophils: altered levels in leukemic neutrophils and changes during myeloid maturation in chronic myeloid leukemia. Leukemia Res 26(1):67–81CrossRefGoogle Scholar
  6. Berger M, Hsieh CY, Bakele M, Marcos V, Rieber N, Kormann M, Mays L, Hofer L, Neth O, Vitkov L, Krautgartner WD, von Schweinitz D, Kappler R, Hector A, Weber A, Hartl D (2012) Neutrophils express distinct RNA receptors in a non-canonical way. J Biol Chem 287(23): 19409–19417PubMedPubMedCentralCrossRefGoogle Scholar
  7. Biasi D, Carletto A, Dellagnola C et al (1996) Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 20(6):673–681PubMedCrossRefGoogle Scholar
  8. Bleharski JR, Kiessler V, Buonsanti C, Sieling PA, Stenger S, Colonna M, Modlin RL (2003) A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol 170(7):3812–3818PubMedCrossRefGoogle Scholar
  9. Bouchon A, Dietrich J, Colonna M (2000) Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 164(10): 4991–4995PubMedCrossRefGoogle Scholar
  10. Camps M, Carozzi A, Schnabel P, Scheer A, Parker PJ, Gierschik P (1992) Isozyme-selective stimulation of phospholipase C-b2 by G protein b g subunits. Nature 360(6405):684–689PubMedCrossRefGoogle Scholar
  11. Cannon JP, O’Driscoll M, Litman GW (2012) Specific lipid recognition is a general feature of CD300 and TREM molecules. Immunogenetics 64(1):39–47PubMedCrossRefGoogle Scholar
  12. Chang LC, Wang JP (1999) Examination of the signal transduction pathways leading to activation of extracellular signal-regulated kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. FEBS Lett 454(1–2):165–168PubMedCrossRefGoogle Scholar
  13. Chang LC, Wang JP (2000) Activation of p38 mitogen-activated protein kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. Eur J Pharmacol 390(1–2):61–66PubMedCrossRefGoogle Scholar
  14. Cloutier A, Ear T, Blais-Charron E, Dubois CM, McDonald PP (2007) Differential involvement of NF-kappaB and MAP kinase pathways in the generation of inflammatory cytokines by human neutrophils. J Leukoc Biol 81(2):567–577PubMedCrossRefGoogle Scholar
  15. Dalboni TM, Abe AE, de Oliveira CE, Lara VS, Campanelli AP, Gasparoto CT, Gasparoto TH (2013) Activation profile of CXCL8-stimulated neutrophils and aging. Cytokine 61(3):716–719PubMedCrossRefGoogle Scholar
  16. Ear T, Fortin CF, Simard A et al (2010) Constitutive association of TGF-beta-activated kinase 1 with the IkappaB kinase complex in the nucleus and cytoplasm of human neutrophils and its impact on downstream processes. J Immunol 184(7):3897–3906PubMedCrossRefGoogle Scholar
  17. Epling-Burnette PK, Zhong B, Bai F, Jiang K, Bailey RD, Garcia R, Jove R, Djeu JY, Loughran TP Jr, Wei S (2001) Cooperative regulation of Mcl-1 by Janus kinase/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils. J Immunol 166(12):7486–95Google Scholar
  18. Fortin C, Fulop T (2015) Isolation of lipid rafts from human neutrophils by density gradient centrifugation. Methods Mol Biol 1343:1–7PubMedCrossRefGoogle Scholar
  19. Fortin CF, Larbi A, Lesur O, Douziech N, Fulop T (2006) Impairment of SHP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions. J Leukoc Biol 79(5):1061–1072PubMedCrossRefGoogle Scholar
  20. Fortin CF, Larbi A, Dupuis G, Lesur O, Fulop T (2007a) GM-CSF activates the Jak/STAT pathway to rescue polymorphonuclear neutrophils from spontaneous apoptosis in young but not elderly individuals. Biogerontology 8(2):173–187PubMedCrossRefGoogle Scholar
  21. Fortin CF, Lesur O, Fulop T (2007b) Effects of TREM-1 activation in human neutrophils: activation of signaling pathways, recruitment into lipid rafts and association with TLR4. Int Immunol 19(1):41–50PubMedCrossRefGoogle Scholar
  22. Fortin CF, Lesur O, Fulop T (2007c) Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions. FEBS Lett 581(6):1173–1178PubMedCrossRefGoogle Scholar
  23. Fortin CF, McDonald PP, Lesur O, Fülöp T Jr (2008) Aging and neutrophils: there is still much to do. Rejuvenation Res 11(5):873–882PubMedCrossRefGoogle Scholar
  24. Fortin CF, Cloutier A, Ear T, Sylvain-Prévost S, Mayer TZ, Bouchelaghem R, McDonald PP (2011) A class IA PI3K controls inflammatory cytokine production in human neutrophils. Eur J Immunol 41(6):1709–1719PubMedCrossRefGoogle Scholar
  25. Fortin CF, Mayer TZ, Cloutier A, McDonald PP (2013) Translational control of human neutrophil responses by MNK1. J Leukoc Biol 94(4):693–703PubMedCrossRefGoogle Scholar
  26. Fu H, Karlsson J, Bylund J, Movitz C, Karlsson A, Dahlgren C (2006) Ligand recognition and activation of formyl peptide receptors in neutrophils. J Leukoc Biol 79(2):247–256PubMedCrossRefGoogle Scholar
  27. Fülöp T Jr, Fóris G, Wórum I, Leövey A (1985) Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes. Clin Exp Immunol 61(2):425–432PubMedPubMedCentralGoogle Scholar
  28. Fulop T Jr, Fouquet C, Allaire P, Perrin N, Lacombe G, Stankova J, Rola-Pleszczinsky M, Wagner JR, Khalil A, Dupuis G (1997) Changes in apoptosis of human polymorphonuclear granulocytes with ageing. Mech Ageing Dev 96(1–3):15–31PubMedCrossRefGoogle Scholar
  29. Fulop T, Larbi A, Douziech N, Fortin CF, Guerard KP, Lesur O, Khalil A, Dupuis G, Fulop T (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell 3(4):217–226PubMedCrossRefGoogle Scholar
  30. Futosi K, Fodor S, Mócsai A (2013) Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol 17(3):638–650PubMedPubMedCentralCrossRefGoogle Scholar
  31. Geijsen N, Koenderman L, Coffer PJ (2001) Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF. Cytokine Growth Factor Rev 12(1):19–25PubMedCrossRefGoogle Scholar
  32. Gibot S (2006) The therapeutic potential of TREM-1 modulation in the treatment of sepsis and beyond. Curr Opin Investig Drugs 7(5):438–442PubMedGoogle Scholar
  33. Gibot S, Kolopp-Sarda MN, Bene MC, Cravoisy A, Levy B, Faure GC, Bollaert PE (2004) Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis. Ann Intern Med 141(1):9–15PubMedCrossRefGoogle Scholar
  34. Gibot S, Buonsanti C, Massin F, Romano M, Kolopp-Sarda MN, Benigni F, Faure GC, Béné MC, Panina-Bordignon P, Passini N, Lévy B (2006) Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock. Infect Immun 74(5):2823–2830PubMedPubMedCentralCrossRefGoogle Scholar
  35. Gierschik P, Sidoropoulos D, Jakobs KH (1989) Two distinct Gi-proteins mediate formyl peptide receptor signal transduction in human leukemia (HL-60) cells. J Biol Chem 264(36): 21470–21473PubMedGoogle Scholar
  36. Hazeldine J, Harris P, Chapple IL, Grant M, Greenwood H, Livesey A, Sapey E, Lord JM (2014) Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals. Aging Cell 13(4):690–698PubMedPubMedCentralCrossRefGoogle Scholar
  37. Indelicato SR, Udupa KB, Balazovich KJ, Boxer LA, Lipschitz DA (1990) Effect of age on phorbol-ester stimulation of human neutrophils. J Gerontol 45(3):B75–B80PubMedCrossRefGoogle Scholar
  38. Juss JK, Hayhoe RP, Owen CE, Bruce I, Walmsley SR, Cowburn AS, Kulkarni S, Boyle KB, Stephens L, Hawkins PT, Chilvers ER, Condliffe AM (2012) Functional redundancy of class I phosphoinositide 3-kinase (PI3K) isoforms in signaling growth factor-mediated human neutrophil survival. PLoS One 7(9):e45933PubMedPubMedCentralCrossRefGoogle Scholar
  39. Kalyan S, Kabelitz D (2014) When neutrophils meet T cells: beginnings of a tumultuous relationship with underappreciated potential. Eur J Immunol 44(3):627–633PubMedCrossRefGoogle Scholar
  40. Kindzelskii AL, Sitrin RG, Petty HR (2004) Cutting edge: optical microspectrophotometry supports the existence of gel phase lipid rafts at the lamellipodium of neutrophils: apparent role in calcium signaling. J Immunol 172(8):4681–5Google Scholar
  41. Klein JB, Rane MJ, Scherzer JA, Coxon PY, Kettritz R, Methiesen JM, Buridi A, McLeish KR (2000) Granulocyte-macrophage colony stimulating factor delays neutrophil constitutive apoptosis through phosphoinositide 3-kinase and extracellular signal regulated kinase pathways. J Immunol 164(8):4286–4291PubMedCrossRefGoogle Scholar
  42. Krishnan J, Selvarajoo K, Tsuchiya M, Lee G, Choi S (2007) Toll-like receptor signal transduction. Exp Mol Med 39(4):421–438PubMedCrossRefGoogle Scholar
  43. Kroemer G, Dallaporta B, Resche-Rigon M (1998) The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60:619–642PubMedCrossRefGoogle Scholar
  44. Kushner EJ, MacEneaney OJ, Weil BR et al (2011) Aging is associated with a proapoptotic endothelial progenitor cell phenotype. J Vasc Res 48(5):408–414PubMedPubMedCentralCrossRefGoogle Scholar
  45. Larbi A, Douziech N, Dupuis G, Khalil A, Pelletier H, Guérard KP, Fülöp T Jr (2004a) Age-associated alterations in the recruitment of signal transduction proteins to lipid rafts in human T lymphocytes. J Leukoc Biol 75(2):373–381PubMedCrossRefGoogle Scholar
  46. Larbi A, Douziech N, Khalil A, Dupuis G, Gheraïri S, Guérard P, Fülöp T Jr (2004b) Effects of Methyl-β-cyclodextrin on T lymphocytes lipid rafts with ageing. Exp Gerontol 39(4):551–558Google Scholar
  47. Larbi A, Douziech N, Fortin CF, Linteau A, Dupuis G, Fulop T (2005) The role of the MAPK pathway alterations in GM-CSF modulated human neutrophil apoptosis with aging. Immun Ageing 2(1):6PubMedPubMedCentralCrossRefGoogle Scholar
  48. Larbi A, Dupuis G, Khalil A, Douziech N, Fortin CF, Fulop T (2006) Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging. Cell Signal 18(7): 1017–1030PubMedCrossRefGoogle Scholar
  49. Larbi A, Fortin C, Dupuis G, Berrougui H, Khalil A, Fulop T (2014) Immunomodulatory role of high-density lipoproteins: impact on immunosenescence. Age 36(5):9712–9717PubMedPubMedCentralCrossRefGoogle Scholar
  50. Lipschitz DA, Udupa KB, Boxer LA (1988) The role of calcium in the age-related decline of neutrophil function. Blood 71(3):659–695PubMedGoogle Scholar
  51. Lorent JH, Levental I (2015) Structural determinants of protein partitioning into ordered membrane domains and lipid rafts. Chem Phys Lipids 192:23–32PubMedCrossRefGoogle Scholar
  52. Mayer TZ, Simard FA, Cloutier A, Vardhan H, Dubois CM, McDonald PP (2013) The p38-MSK1 signaling Cascade influences cytokine production through CREB and C/EBP factors in human neutrophils. J Immunol 191(8):4299–4307PubMedCrossRefGoogle Scholar
  53. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1(2):135–145PubMedCrossRefGoogle Scholar
  54. Miller EJ, Linge HM (2017) Age-related changes in immunological and physiological responses following pulmonary challenge. Int J Mol Sci 18(6):1294PubMedCentralCrossRefGoogle Scholar
  55. Montgomery RR, Shaw AC (2015) Paradoxical changes in innate immunity in aging: recent progress and new directions. J Leukoc Biol 98(6):937–943PubMedPubMedCentralCrossRefGoogle Scholar
  56. Moulding DA, Quayle JA, Hart CA, Edwards SW (1998) Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood 92(7):2495–502Google Scholar
  57. Monti D, Ostan R, Borelli V, Castellani G, Franceschi C (2016) Inflammaging and human longevity in the omics era. Mech Ageing Dev 165:129PubMedCrossRefGoogle Scholar
  58. Nakata Y, Tomkowicz B, Gewirtz AM, Ptasznik A (2006) Integrin inhibition through Lyn-dependent cross talk from CXCR4 chemokine receptors in normal human CD34+ marrow cells. Blood 107(11):4234–4239PubMedPubMedCentralCrossRefGoogle Scholar
  59. Odobasic D, Kitching AR, Holdsworth SR (2016) Neutrophil-mediated regulation of innate and adaptive immunity: the role of myeloperoxidase. J Immunol Res 2016:2349817PubMedPubMedCentralCrossRefGoogle Scholar
  60. Ornatowska M, Azim AC, Wang X, Christman JW, Xiao L, Joo M, Sadikot RT (2007) Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages. Am J Physiol Lung Cell Mol Physiol 293(6):L1377–L1384PubMedPubMedCentralCrossRefGoogle Scholar
  61. Qian F, Guo X, Wang X et al (2014) Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging. Aging (Albany NY) 6(2):131–139CrossRefGoogle Scholar
  62. Radsak MP, Salih HR, Rammensee HG, Schild H (2004) Triggering receptor expressed on myeloid cells-1 in neutrophil inflammatory responses: differential regulation of activation and survival. J Immunol 172(8):4956–4963PubMedCrossRefGoogle Scholar
  63. Rao KMK, Currie MS, Padmadabhan J, Cohen HJ (1992) Age-related alterations in actin cytoskeleton and receptor expression in human leukocytes. J Gerontol 47(2):B37–B44PubMedCrossRefGoogle Scholar
  64. Read CB, Kuijper JL, Hjorth SA, Heipel MD, Tang X, Fleetwood AJ, Dantzler JL, Grell SN, Kastrup J, Wang C, Brandt CS, Hansen AJ, Wagtmann NR, Xu W, Stennicke VW (2015) Cutting edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1. J Immunol 194(4):1417–1421PubMedPubMedCentralCrossRefGoogle Scholar
  65. Rivnay B, Bergman S, Shinitzky M, Globerson A (1980) Correlations between membrane viscosity, serum cholesterol, lymphocytes activation and ageing in man. Mech Ageing Dev 12(2):119–126PubMedCrossRefGoogle Scholar
  66. Ruiz-Pachecoa JA, Vivanco-Cidc H, Izaguirre-Hernándezc IY, Estrada-Garcíab I, Arriaga-Pizanod L, Chacón-Salinasb R, Fonseca-Coronadoe S, Vaughana G, Ruiz Tovara K, Rivera-Sato N, Sakamaki K, Terada N, Arai K, Miyajima A (1993) Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signalling. EMBO J 12(11):4181–4189CrossRefGoogle Scholar
  67. Ruiz-Pacheco JA, Vivanco-Cid H, Izaguirre-Hernández IY, Estrada-García I, Arriaga-Pizano L, Chacón-Salinas R, Fonseca-Coronado S, Vaughan G, Tovar KR, Rivera-Osorio MP, Escobar-Gutiérrez A (2014) TREM-1 modulation during early stages of dengue virus infection. Immunol Lett 158(1–2):183–188Google Scholar
  68. Sakamoto E1, Hato F, Kato T, Sakamoto C, Akahori M, Hino M, Kitagawa S (2005) Type I and type II interferons delay human neutrophil apoptosis via activation of STAT3 and up-regulation of cellular inhibitor of apoptosis 2. J Leukoc Biol 78(1):301–9Google Scholar
  69. Shaw AC, Goldstein DR, Montgomery RR (2013) Age-dependent dysregulation of innate immunity. Nat Rev Immunol 13(12):875–887PubMedPubMedCentralCrossRefGoogle Scholar
  70. Simard FA, Cloutier A, Ear T, Vardhan H, McDonald PP (2015) MEK-independent ERK activation in human neutrophils and its impact on functional responses. J Leukoc Biol 98(4):565–573PubMedCrossRefGoogle Scholar
  71. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387(6633):569–572PubMedCrossRefGoogle Scholar
  72. Sitrin RG, Johnson DR, Pan PM, Harsh DM, Huang J, Petty HR, Blackwood RA (2004) Lipid rafts compartmentalization of urokinase receptor signalling in human neutrophils. Am J Respir Cell Mol Biol 30(2):233–241PubMedCrossRefGoogle Scholar
  73. Shen Y, Devgan G, Darnell JE Jr, Bromberg JF (2001) Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1. Proc Natl Acad Sci USA 98(4):1543–8Google Scholar
  74. Shinitzky M (1987) Patterns of lipid changes in membranes of the aged brain. Gerontology 33(3-4):149–54Google Scholar
  75. Stoyanov B, Volinia S, Hanck T, Rubio I, Loubtchenkov M, Malek D, Stoyanova S, Vanhaesebroeck B, Dhand R, Nurnberg B, Gierschik P, Seedorf K, Hsuan JJ, Waterfield MD, Wetzker R (1995) Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science 269(5224):690–693PubMedCrossRefGoogle Scholar
  76. Sylvain-Prevost S, Ear T, Simard FA, Fortin C, Dubois CM, Flamand N, McDonald PP (2015) Activation of TAK1 by chemotactic and growth factors, and its impact on human neutrophil signaling and functional responses. J Immunol 195(11):5393–5403PubMedCrossRefGoogle Scholar
  77. Tamassia N, Le Moigne V, Calzetti F, Donini M, Gasperini S, Ear T, Cloutier A, Martinez FO, Fabbri M, Locati M, Mantovani A, McDonald PP, Cassatella M (2007) The MyD88-independent pathway is not mobilized in human neutrophils stimulated via TLR4. J Immunol 178(11):7344–7356PubMedCrossRefGoogle Scholar
  78. Tortorella C, Piazzolla G, Spaccavento F, Pece S, Jirillo E, Antonaci S (1998) Spontaneous and Fas induced apoptotic cell death in aged neutrophils. J Clin Immunol 18(5):321–329PubMedCrossRefGoogle Scholar
  79. Tortorella C, Stella I, Piazzolla G, Simone O, Cappiello V, Antonaci S (2004) Role of defective ERK phosphorylation in the impaired GM-CSF-induced oxidative response of neutrophils in elderly humans. Mech Ageing Dev 125(8):539–546PubMedCrossRefGoogle Scholar
  80. Tortorella C, Simone O, Piazzolla G, Stella I, Cappiello V, Antonaci S (2006) Role of phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways in granulocyte macrophage–colony-stimulating factor failure to delay Fas-induced neutrophil apoptosis in elderly humans. J Gerontol A Biol Sci Med Sci 61(11):1111–1118PubMedCrossRefGoogle Scholar
  81. Tortorella C, Simone O, Piazzolla G, Stella I, Antonaci S (2007) Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. Ageing Res Rev 6(2):81–93PubMedCrossRefGoogle Scholar
  82. Valayer A, Brea D, Lajoie L, Avezard L, Combes-Soia L, Labas V, Korkmaz B, Thibault G, Baranek T, Si-Tahar M (2017) Neutrophils can disarm NK cell response through cleavage of NKp46. J Leukoc Biol 101(1):253–259PubMedCrossRefGoogle Scholar
  83. Watanabe S, Itoh T, Arai K (1997) Roles of JAK kinase in human GM-CSF receptor signals. Leukemia 11(S3):76–78PubMedGoogle Scholar
  84. Zu YL, Qi J, Gilchrist A, Fernandez GA, Vazquez-Abad D, Kreutze DL, Huang CK, Sha’afi RI (1998) p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-alpha or fMLP stimulation. J Immunol 160(4):1982–1989PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Carl Fortin
    • 1
    Email author
  • Tamas Fulop
    • 1
  • Anis Larbi
    • 2
  • Gilles Dupuis
    • 3
  1. 1.Division of Geriatric Medicine, Department of Medicine, Research Center on AgingUniversité de SherbrookeSherbrookeCanada
  2. 2.Singapore Immunology Network (SIgN), Aging and Immunity ProgramAgency for Science Technology and Research (A*STAR)SingaporeSingapore
  3. 3.Immunology Programme, Department of Biochemistry, Faculty of Medicine and Health SciencesUniversity of SherbrookeSherbrookeCanada

Personalised recommendations