Advertisement

Basophil, Eosinophil, and Neutrophil Functions in the Elderly

  • Peter Uciechowski
  • Lothar RinkEmail author
Chapter

Abstract

Human granulocytes are classically characterized by their capacity to act as phagocytes, degranulators secreting preformed lytic enzymes from their granules, and produce reactive oxygen species (ROS) to destroy bacteria, parasites, and fungi. Basophils and eosinophils are mainly involved in the defense against parasites or allergic reactions, but also they play important roles in antigen presentation, immune memory response, and T helper 2 cell (Th2) differentiation. Like basophils and eosinophils, neutrophils and their function have been underestimated in research for a long time. Thus, neutrophils have been categorized as short-lived phagocytic cells of the innate immune system with limited ability for biosynthetic activity and being the first cells appearing in inflamed locations/acute inflammation to fight extracellular pathogens. In the last two decades, this limited view was challenged by the demonstration that neutrophils survive much longer than first suggested and can be induced to de novo express genes encoding key inflammatory mediators, including complement components, Fc receptors, chemokines, and cytokines. Immune cells of the innate and the adaptive system are uniformly compromised by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. Whereas the effects of aging on T and B cells of the adaptive immune system are well documented, studies related to age-related defects of polymorphonuclear neutrophils (PMN), basophils, and eosinophils are restricted. That is surprising since genetically induced immune defects of, e.g., neutrophils increase susceptibility to severe infections and mortality. Furthermore, during aging there is a shift from the adaptive immune to the innate system which raises the importance of these cells. There is consensus about unchanged neutrophil numbers in the circulation throughout aging; apart from this, reports about changes in tissue infiltration, phagocytosis, and burst capabilities of neutrophils from aged donors are inconsistent. Additionally, there are many different results between in vivo and in vitro studies as well as between studies investigating murine and human neutrophils. The majority of the reported discrepancies in neutrophils during aging function originate from damaged signaling pathways and studies where the SENIEUR protocol has not been used. Research in neutrophils, in addition, would build the basis for drug development in preventing and/or fighting age-related diseases. Research on human basophils and eosinophils and their function during aging is rare despite the fact that these cells are important in defense against parasites and play an important role in allergy, asthma, and autoimmune diseases. This chapter highlights the age-related changes of the immune system, focusing on new insights into neutrophil, basophil, and eosinophil immunity.

Keywords

Reactive Oxygen Species Production Lipid Raft Respiratory Burst Aged Donor Young Donor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Adamko DJ, Odemuyiwa SO, Vethanayagam D et al (2005) The rise of the phoenix: the expanding role of the eosinophil in health and disease. Allergy 60:13–22PubMedGoogle Scholar
  2. Agrawal A, Gupta S (2011) Impact of aging on dendritic cell functions in humans. Ageing Res Rev 10:336–345PubMedGoogle Scholar
  3. Agrawal A, Agrawal S, Gupta S (2007) Dendritic cells in human aging. Exp Gerontol 42:421–426PubMedGoogle Scholar
  4. Alonso-Fernandez P, Puerto M, Mate I et al (2008) Neutrophils of centenarians show function levels similar to those of young adults. J Am Geriatr Soc 56:2244–2251PubMedGoogle Scholar
  5. Altstaedt J, Kirchner H, Rink L (1996) Cytokine production of neutrophils is limited to interleukin-8. Immunology 89:563–568PubMedGoogle Scholar
  6. Alvarez E, Ruiz-Gutierrez V, Sobrino F et al (2001) Age-related changes in membrane lipid composition, fluidity and respiratory burst in rat peritoneal neutrophils. Clin Exp Immunol 124:95–102PubMedGoogle Scholar
  7. Antonaci S, Jirillo E, Ventura MT et al (1984) Non-specific immunity in aging-deficiency of monocyte and polymorphonuclear cell-mediated functions. Mech Ageing Dev 24:367–375PubMedGoogle Scholar
  8. Barthel SR, Johansson MW, McNamee DM et al (2008) Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma. J Leukoc Biol 83:1–12PubMedGoogle Scholar
  9. Behm CA, Ovington KS (2000) The role of eosinophils in parasitic helminth infections insights from genetically modified mice. Parasitol Today 16:202–209PubMedGoogle Scholar
  10. Bhushan M, Cumberbatch M, Dearman RJ et al (2002) Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the influence of ageing. Br J Dermatol 146:32–40PubMedGoogle Scholar
  11. Biasi D, Carletto A, Dellagnola C et al (1996) Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 20:673–681PubMedGoogle Scholar
  12. Boehmer ED, Goral J, Faunce DE et al (2004) Age-dependent decrease in toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J Leukoc Biol 75:342–349PubMedGoogle Scholar
  13. Born J, Uthgenannt D, Dodt C et al (1995) Cytokine production and lymphocyte subpopulations in aged humans. An assessment during nocturnal sleep. Mech Ageing Dev 84:113–126PubMedGoogle Scholar
  14. Borregaard N, Sorensen OE, Theilgaard-Wnchl K (2007) Neutrophil granules: a library of innate immunity proteins. Trends Immunol 28:340–345PubMedGoogle Scholar
  15. Braga PC, Sala MT, Dal Sasso M et al (1998) Influence of age on oxidative bursts (chemiluminescence) of polymorphonuclear neutrophil leukocytes. Gerontology 44:192–197PubMedGoogle Scholar
  16. Busse PJ, Mathur SK (2010) Age-related changes in immune function: effect on airway inflammation. J Allergy Clin Immunol 126:690–699PubMedGoogle Scholar
  17. Butcher S, Chahel H, Lord JM (2000) Ageing and the neutrophil: no appetite for killing? Immunology 100:411–416PubMedGoogle Scholar
  18. Butcher SK, Chahal H, Nayak L et al (2001) Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol 70:881–886PubMedGoogle Scholar
  19. Cakman I, Kirchner H, Rink L (1997) Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons. J Interferon Cytokine Res 17:469–472PubMedGoogle Scholar
  20. Cassatella MA (1995) The production of cytokines by polymorphonuclear neutrophils. Immunol Today 16:21–26PubMedGoogle Scholar
  21. Chatta GS, Andrews RG, Rodger E et al (1993) Hematopoietic progenitors and aging-alterations in granulocytic precursors and responsiveness to recombinant human G-Csf, Gm-Csf, and Il-3. J Gerontol 48:M207–M212PubMedGoogle Scholar
  22. Chaves MM, Costa DC, Pereira CCT et al (2007) Role of inositol 1,4,5-triphosphate and p38 mitogen-activated protein kinase in reactive oxygen species generation by granulocytes in a cyclic AMP-dependent manner: an age-related phenomenon. Gerontology 53:228–233PubMedGoogle Scholar
  23. Damtew B, Spagnuolo PJ, Goldsmith GGH et al (1990) Neutrophil adhesion in the elderly – inhibitory effects of plasma from elderly patients. Clin Immunol Immunopathol 54:247–255PubMedGoogle Scholar
  24. De Martinis M, Modesti M, Ginaldi L (2004) Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol 82:415–420PubMedGoogle Scholar
  25. Denzel A, Maus UA, Gomez MR et al (2008) Basophils enhance immunological memory responses. Nat Immunol 9:733–742PubMedGoogle Scholar
  26. Di Lorenzo G, Balistreri CR, Candore G et al (1999) Granulocyte and natural killer activity in the elderly. Mech Ageing Dev 108:25–38PubMedGoogle Scholar
  27. Di Lorenzo G, Pacor ML, Pellitteri ME et al (2003) A study of age-related IgE pathophysiological changes. Mech Ageing Dev 124:445–448PubMedGoogle Scholar
  28. Di Lorenzo G, Leto-Barone MS, La Piana S et al (2012) Clinical course of rhinitis and changes in vivo and in vitro of allergic parameters in elderly patients: a long-term follow-up study. Clin Exp Med 13(1):67–73PubMedGoogle Scholar
  29. Egger G, Burda A, Mitterhammer H et al (2003) Impaired blood polymorphonuclear leukocyte migration and infection risk in severe trauma. J Infect 47:148–154PubMedGoogle Scholar
  30. Esparza B, Sanchez H, Ruiz M et al (1996) Neutrophil function in elderly persons assessed by flow cytometry. Immunol Invest 25:185–190PubMedGoogle Scholar
  31. Fanger NA, Liu CL, Guyre PM et al (1997) Activation of human T cells by major histocompatibility complex class II expressing neutrophils: proliferation in the presence of superantigen, but not tetanus toxoid. Blood 89:4128–4135PubMedGoogle Scholar
  32. Ferretti S, Bonneau O, Dubois GR et al (2003) IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger. J Immunol 170:2106–2112PubMedGoogle Scholar
  33. Fortin CF, Larbi A, Lesur O et al (2006) Impairment of SHIP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions. J Leukoc Biol 79:1061–1072PubMedGoogle Scholar
  34. Fortin CF, Lesur O, Fulop T (2007a) Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions. FEBS Lett 581:1173–1178PubMedGoogle Scholar
  35. Fortin CF, Larbi A, Dupuis G et al (2007b) GM-CSF activates the Jak/STAT pathway to rescue polymorphonuclear neutrophils from spontaneous apoptosis in young but not elderly individuals. Biogerontology 8:173–187PubMedGoogle Scholar
  36. Fortin CF, Lesur O, Fulop T (2007c) Effects of TREM-1 activation in human neutrophils: activation of signaling pathways, recruitment into lipid rafts and association with TLR4. Int Immunol 19:41–50PubMedGoogle Scholar
  37. Fortin CF, McDonald PP, Lesur O et al (2008) Aging and neutrophils: there is still much to do. Rejuvenation Res 11:873–882PubMedGoogle Scholar
  38. Fortin CF, Larbi A, Dupuis G et al (2009a) Signal transduction changes in fMLP, TLRs, TREM-1 and GM-CSF receptors in PMN with aging. In: Handbook on immunosenescence. Springer, HeidelbergGoogle Scholar
  39. Fortin CF, Ear T, McDonald PP (2009b) Autocrine role of endogenous interleukin-18 on inflammatory cytokine generation by human neutrophils. FASEB J 23:194–203PubMedGoogle Scholar
  40. Franceschi C, Capri M, Monti D et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105PubMedGoogle Scholar
  41. Fulop T (1994) Signal-transduction changes in granulocytes and lymphocytes with aging. Immunol Lett 40:259–268PubMedGoogle Scholar
  42. Fulop T, Fouquet C, Allaire P et al (1997) Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev 96:15–34PubMedGoogle Scholar
  43. Fulop T, Goulet AC, Desgeorges S et al (1999) Changes in the apoptosis of polymorphonuclear granulocytes with aging. FASEB J 13:A519Google Scholar
  44. Fulop T, Douziech N, Desgeorges S et al (2000a) Signal transduction alterations in the apoptosis of polymorphonuclear granulocytes with aging under GM-CSF stimulation. FASEB J 14:A1156Google Scholar
  45. Fulop T, Douziech N, Desgeorges S et al (2000b) Apoptosis in T lymphocytes and polymorphonuclear leukocytes with aging. FASEB J 14:A194Google Scholar
  46. Fulop T, Larbi A, Douziech N et al (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell 3:217–226PubMedGoogle Scholar
  47. Fulop T, Larbi A, Douziech N et al (2006) Cytokine receptor signalling and aging. Mech Ageing Dev 127:526–537PubMedGoogle Scholar
  48. Fulop T, Kotb R, Fortin CF et al (2010) Potential role of immunosenescence in cancer development. Ann N Y Acad Sci 1197:158–165PubMedGoogle Scholar
  49. Gabriel P, Cakman I, Rink L (2002) Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. Exp Gerontol 37:235–247PubMedGoogle Scholar
  50. Geiger H, Rudolph KL (2009) Aging in the lympho-hematopoietic stem cell compartment. Trends Immunol 30:360–365PubMedGoogle Scholar
  51. Ginaldi L, De Martinis M, D’Ostilio A et al (1999) The immune system in the elderly III. Innate immunity. Immunol Res 20:117–126PubMedGoogle Scholar
  52. Gomez CR, Hirano S, Cutro BT et al (2007) Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure. Crit Care Med 35:246–251PubMedGoogle Scholar
  53. Gomez CR, Nomellini V, Faunce DE et al (2008) Innate immunity and aging. Exp Gerontol 43:718–728PubMedGoogle Scholar
  54. Gosselin EJ, Wardwell K, Rigby WFC et al (1993) Induction of Mhc class-Ii on human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor, Ifn-gamma, and Il-3. J Immunol 151:1482–1490PubMedGoogle Scholar
  55. Grubeck-Loebenstein B, Della Bella S, Iorio AM et al (2009) Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 21:201–209PubMedGoogle Scholar
  56. Gunin AG, Kornilova NK, Vasilieva OV et al (2011) Age-related changes in proliferation, the numbers of mast cells, eosinophils, and CD45-positive cells in human dermis. J Gerontol A Biol Sci Med Sci 66:385–392PubMedGoogle Scholar
  57. Haase H, Rink L (2009) Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr 29:133–152PubMedGoogle Scholar
  58. Haase H, Mocchegiani E, Rink L (2006) Correlation between zinc status and immune function in the elderly. Biogerontology 7:421–428PubMedGoogle Scholar
  59. Hannah S, Mecklenburgh K, Rahman I et al (1995) Hypoxia prolongs neutrophil survival in-vitro. FEBS Lett 372:233–237PubMedGoogle Scholar
  60. Hellewell PG, Williams TJ (1994) The neutrophil. In: The handbook of immunopharmacology: immunopharmacology of neutrophils. Academic, LondonGoogle Scholar
  61. Hogan SP, Rosenberg HF, Moqbel R et al (2008) Eosinophils: biological properties and role in health and disease. Clin Exp Allergy 38:709–750PubMedGoogle Scholar
  62. Iking-Konert C, Wagner C, Denefleh B et al (2002) Up-regulation of the dendritic cell marker CD83 on polymorphonuclear neutrophils (PMN): divergent expression in acute bacterial infections and chronic inflammatory disease. Clin Exp Immunol 130:501–508PubMedGoogle Scholar
  63. Issa JP (2003) Age-related epigenetic changes and the immune system. Clin Immunol 109:103–108PubMedGoogle Scholar
  64. Ito Y, Kajkenova O, Feuers RJ et al (1998) Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils. J Gerontol A Biol Sci Med Sci 53:M169–M175PubMedGoogle Scholar
  65. Kim KC, Friso S, Choi SW (2009) DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging. J Nutr Biochem 20:917–926PubMedGoogle Scholar
  66. Kita H (2011) Eosinophils: multifaceted biological properties and roles in health and disease. Immunol Rev 242:161–177PubMedGoogle Scholar
  67. Klut ME, Ruehlmann DO, Li L et al (2002) Age-related changes in the calcium homeostasis of adherent neutrophils. Exp Gerontol 37:533–541PubMedGoogle Scholar
  68. Kovacs EJ, Palmer JL, Fortin CF et al (2009) Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol 30:319–324PubMedGoogle Scholar
  69. Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda) 23:64–74Google Scholar
  70. Laupland KB, Church DL, Mucenski M et al (2003) Population-based study of the epidemiology of and the risk factors for invasive Staphylococcus aureus infections. J Infect Dis 187:1452–1459PubMedGoogle Scholar
  71. Leng SX, Xue QL, Huang Y et al (2005) Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women. Exp Gerontol 40:982–987PubMedGoogle Scholar
  72. Leng SX, Xue QL, Tian J et al (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55:864–871PubMedGoogle Scholar
  73. Leng SX, Xue QL, Tian J et al (2009) Associations of neutrophil and monocyte counts with frailty in community-dwelling disabled older women: results from the Women’s Health and Aging Studies I. Exp Gerontol 44:511–516PubMedGoogle Scholar
  74. Ligthart GJ, Corberand JX, Fournier C et al (1984) Admission criteria for immunogerontological studies in man – the Senieur protocol. Mech Ageing Dev 28:47–55PubMedGoogle Scholar
  75. Lipschitz DA, Udupa KB, Indelicato SR et al (1991) Effect of age on 2Nd messenger generation in neutrophils. Blood 78:1347–1354PubMedGoogle Scholar
  76. Lloyd AR, Oppenheim JJ (1992) Polys lament – the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune-response. Immunol Today 13:169–172PubMedGoogle Scholar
  77. Lord JM, Butcher S, Killampali V et al (2001) Neutrophil ageing and immunesenescence. Mech Ageing Dev 122:1521–1535PubMedGoogle Scholar
  78. Mahbub S, Brubaker AL, Kovacs EJ (2011) Aging of the innate immune system: an update. Curr Immunol Rev 7:104–115PubMedGoogle Scholar
  79. Mantovani A, Cassatella MA, Costantini C et al (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531PubMedGoogle Scholar
  80. Marone G, Poto S, Dimartino L et al (1986) Human basophil releasability.1. Age-related-changes in basophil releasability. J Allergy Clin Immunol 77:377–383PubMedGoogle Scholar
  81. Mathur SK, Schwantes EA, Jarjour NN et al (2008) Age-related changes in eosinophil function in human subjects. Chest 133:412–419PubMedGoogle Scholar
  82. Mclaughlin B, Omalley K, Cotter TG (1986) Age-related differences in granulocyte chemotaxis and degranulation. Clin Sci 70:59–62PubMedGoogle Scholar
  83. Min B, Brown MA, LeGros G (2012) Understanding the roles of basophils: breaking dawn. Immunology 135:192–197PubMedGoogle Scholar
  84. Mohacsi A, Fulop T, Kozlovszky B et al (1992) Superoxide anion production and intracellular free calcium levels in resting and stimulated polymorphonuclear leukocytes obtained from healthy and arteriosclerotic subjects of various ages. Clin Biochem 25:285–288PubMedGoogle Scholar
  85. Muniz VS, Weller PF, Neves JS (2012) Eosinophil crystalloid granules: structure, function, and beyond. J Leukoc Biol 92:281–288PubMedGoogle Scholar
  86. Murciano C, Yanez A, O’Connor JE et al (2008) Influence of aging on murine neutrophil and macrophage function against Candida albicans. FEMS Immunol Med Microbiol 53:214–221PubMedGoogle Scholar
  87. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173–182PubMedGoogle Scholar
  88. Nel HJ, Hams E, Saunders SP et al (2011) Impaired basophil induction leads to an age-dependent innate defect in type 2 immunity during helminth infection in mice. J Immunol 186:4631–4639PubMedGoogle Scholar
  89. Niwa Y, Kasama T, Miyachi Y et al (1989) Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging – cross-sectional and longitudinal-studies. Life Sci 44:1655–1664PubMedGoogle Scholar
  90. Nomellini V, Faunce DE, Gomez CR et al (2008) An age-associated increase in pulmonary inflammation after burn injury is abrogated by CXCR2 inhibition. J Leukoc Biol 83:1493–1501PubMedGoogle Scholar
  91. Opal SM, Girard TD, Ely EW (2005) The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 41:S504–S512PubMedGoogle Scholar
  92. Panda A, Arjona A, Sapey E et al (2009) Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 30:325–333PubMedGoogle Scholar
  93. Panda A, Qian F, Mohanty S et al (2010) Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol 184:2518–2527PubMedGoogle Scholar
  94. Pawelec G, Larbi A, Derhovanessian E (2010) Senescence of the human immune system. J Comp Pathol 141:S39–S44Google Scholar
  95. Plackett TP, Boehmer ED, Faunce DE et al (2004) Aging and innate immune cells. J Leukoc Biol 76:291–299PubMedGoogle Scholar
  96. Prasad AS, Fitzgerald JT, Hess JW et al (1993) Zinc-deficiency in elderly patients. Nutrition 9:218–224PubMedGoogle Scholar
  97. Prasad AS, Beck FWJ, Bao B et al (2007) Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr 85:837–844PubMedGoogle Scholar
  98. Rao KMK (1986) Age-related decline in ligand-induced actin polymerization in human-leukocytes and platelets. J Gerontol 41:561–566PubMedGoogle Scholar
  99. Rao KMK, Currie MS, Padmanabhan J et al (1992) Age-related alterations in actin cytoskeleton and receptor expression in human-leukocytes. J Gerontol 47:B37–B44PubMedGoogle Scholar
  100. Reato G, Cuffini AM, Tullio V et al (1999) Co-amoxiclav affects cytokine production by human polymorphonuclear cells. J Antimicrob Chemother 43:715–718PubMedGoogle Scholar
  101. Renshaw M, Rockwell J, Engleman C et al (2002) Cutting edge: impaired toll-like receptor expression and function in aging. J Immunol 169:4697–4701PubMedGoogle Scholar
  102. Rink L, Kirchner H (2000) Zinc-altered immune function and cytokine production. J Nutr 130:1407S–1411SPubMedGoogle Scholar
  103. Rink L, Cakman I, Kirchner H (1998) Altered cytokine production in the elderly. Mech Ageing Dev 102:199–209PubMedGoogle Scholar
  104. Routsi C, Stamataki E, Nanas S et al (2008) Increased levels of serum S100B protein in critically ill patients without brain injury – Reply. Shock 30:222–223Google Scholar
  105. Savill JS, Wyllie AH, Henson JE et al (1989) Macrophage phagocytosis of aging neutrophils in inflammation – programmed cell-death in the neutrophil leads to its recognition by macrophages. J Clin Invest 83:865–875PubMedGoogle Scholar
  106. Schröder AK, Rink L (2003) Neutrophil immunity of the elderly. Mech Ageing Dev 124:419–425PubMedGoogle Scholar
  107. Schröder AK, der Ohe M, Kolling U et al (2006a) Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators. Immunology 119:317–327PubMedGoogle Scholar
  108. Schröder AK, Uciechowski P, Fleischer D et al (2006b) Crosslinking of CD66b on peripheral blood neutrophils mediates the release of interleukin-8 from intracellular storage. Hum Immunol 67:676–682PubMedGoogle Scholar
  109. Schwarzenbach HR, Nakagawa T, Conroy MC et al (1982) Skin reactivity, basophil de-granulation and Ige levels in aging. Clin Allergy 12:465–473PubMedGoogle Scholar
  110. Seres I, Csongor J, Mohacsi A et al (1993) Age-dependent alterations of human recombinant Gm-Csf effects on human granulocytes. Mech Ageing Dev 71:143–154PubMedGoogle Scholar
  111. Shaw AC, Joshi S, Greenwood H et al (2010) Aging of the innate immune system. Curr Opin Immunol 22:507–513PubMedGoogle Scholar
  112. Shaw AC, Panda A, Joshi SR et al (2011) Dysregulation of human toll-like receptor function in aging. Ageing Res Rev 10:346–353PubMedGoogle Scholar
  113. Simell B, Vuorela A, Ekstrom N et al (2011) Aging reduces the functionality of anti-pneumococcal antibodies and the killing of Streptococcus pneumoniae by neutrophil phagocytosis. Vaccine 29:1929–1934PubMedGoogle Scholar
  114. Smith P, Dunne DW, Fallon PG (2001) Defective in vivo induction of functional type 2 cytokine responses in aged mice. Eur J Immunol 31:1495–1502PubMedGoogle Scholar
  115. Solana R, Pawelec G, Tarazona R (2006) Aging and innate immunity. Immunity 24:491–494PubMedGoogle Scholar
  116. Song C, Vandewoude M, Stevens W et al (1999) Alterations in immune functions during normal aging and Alzheimer’s disease. Psychiatry Res 85:71–80PubMedGoogle Scholar
  117. Starr JM, Deary IJ (2011) Sex differences in blood cell counts in the Lothian Birth Cohort 1921 between 79 and 87 years. Maturitas 69:373–376PubMedGoogle Scholar
  118. Sullivan BM, Liang HE, Bando JK et al (2011) Genetic analysis of basophil function in vivo. Nat Immunol 12:527–535PubMedGoogle Scholar
  119. Swain SL, Nikolich-Zugich J (2009) Key research opportunities in immune system aging. J Gerontol A Biol Sci Med Sci 64:183–186PubMedGoogle Scholar
  120. Swift ME, Burns AL, Gray KL et al (2001) Age-related alterations in the inflammatory response to dermal injury. J Invest Dermatol 117:1027–1035PubMedGoogle Scholar
  121. Tortorella C, Polignano A, Piazzolla G et al (1996) Lipopolysaccharide-, granulocyte-monocyte colony stimulating factor and pentoxifylline-mediated effects on formyl-methionyl-leucine-phenylalanine-stimulated neutrophil respiratory burst in the elderly. Microbios 85:189–198PubMedGoogle Scholar
  122. Tortorella C, Piazzolla G, Spaccavento F et al (1998) Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis. Mediators Inflamm 7:391–396PubMedGoogle Scholar
  123. Tortorella C, Piazzolla G, Spaccavento F et al (1999) Age-related effects of oxidative metabolism and cyclic AMP signaling on neutrophil apoptosis. Mech Ageing Dev 110:195–205PubMedGoogle Scholar
  124. Tortorella C, Piazzolla G, Spaccavento F et al (2000) Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging. Mech Ageing Dev 119:69–82PubMedGoogle Scholar
  125. Tortorella C, Stella I, Piazzolla G et al (2004) Role of defective ERK phosphorylation in the impaired GM-CSF-induced oxidative response of neutrophils in elderly humans. Mech Ageing Dev 125:539–546PubMedGoogle Scholar
  126. Tortorella C, Simone O, Piazzolla G et al (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 61:1111–1118PubMedGoogle Scholar
  127. Tortorella C, Simone O, Piazzolla G et al (2007) Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. Ageing Res Rev 6:81–93PubMedGoogle Scholar
  128. Uciechowski P, Rink L (2009) Neutrophil granulocyte functions in the elderly. In: Handbook on immunosenescence. Springer, HeidelbergGoogle Scholar
  129. Van Duin D, Shaw AC (2007) Toll-like receptors in older adults. J Am Geriatr Soc 55:1438–1444PubMedGoogle Scholar
  130. Van Panhuys N, Prout M, Forbes E et al (2011) Basophils are the major producers of IL-4 during primary helminth infection. J Immunol 186:2719–2728PubMedGoogle Scholar
  131. Varga Z, Kovacs EM, Paragh G et al (1988) Effect of elastin peptides and N-formyl-methionyl-leucyl phenylalanine on cytosolic free calcium in polymorphonuclear leukocytes of healthy middle-aged and elderly subjects. Clin Biochem 21:127–130PubMedGoogle Scholar
  132. Von der Ohe M, Altstaedt J, Gross U et al (2001) Human neutrophils produce macrophage inhibitory protein-1 beta but not type 1 interferons in response to viral stimulation. J Interferon Cytokine Res 21:241–247PubMedGoogle Scholar
  133. Ward JR, Heath PR, Catto JW et al (2011) Regulation of neutrophil senescence by MicroRNAs. PLoS One 6(1):e15810PubMedGoogle Scholar
  134. Weiskopf D, Weinberger B, Grubeck-Loebenstein B (2009) The aging of the immune system. Transpl Int 22:1041–1050PubMedGoogle Scholar
  135. Wenisch C, Patruta S, Daxbock F et al (2000) Effect of age on human neutrophil function. J Leukoc Biol 67:40–45PubMedGoogle Scholar
  136. Wessels I, Fleischer D, Rink L et al (2010a) Changes in chromatin structure and methylation of the human interleukin-1 beta gene during monopoiesis. Immunology 130:410–417PubMedGoogle Scholar
  137. Wessels I, Jansen J, Rink L et al (2010b) Immunosenescence of polymorphonuclear neutrophils. ScientificWorldJournal 10:145–160PubMedGoogle Scholar
  138. Wessels I, Haase H, Engelhardt G et al (2013) Zinc deficiency induces production of the proinflammatory cytokines IL-1β and TNFα in promyeloid cells via epigenetic and redox-dependent mechanisms. J Nutr Biochem 24(1):289–297PubMedGoogle Scholar
  139. Whitelaw DA, Rayner BL, Willcox PA (1992) Community-acquired bacteremia in the elderly – a prospective-study of 121 cases. J Am Geriatr Soc 40:996–1000PubMedGoogle Scholar
  140. Yagi T, Sato A, Hayakawa H et al (1997) Failure of aged rats to accumulate eosinophils in allergic inflammation of the airway. J Allergy Clin Immunol 99:38–47PubMedGoogle Scholar
  141. Yoshimoto T, Yasuda K, Tanaka H et al (2009) Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4(+) T cells. Nat Immunol 10:706–712PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute of ImmunologyMedical Faculty of the RWTH Aachen UniversityAachenGermany

Personalised recommendations