Skip to main content
SpringerLink
Log in

Neutrophil Granulocyte Functions in the Elderly

  • Chapter
Handbook on Immunosenescence

  • 1855 Accesses

Abstract

The immune response weakens during aging. Especially, the altered functions of the lymphocytes of the adaptive immune system have been extensively studied. Aged persons > 65 years display a predisposition to inflammation and infection combined with an increase in morbidity and mortality than younger individuals. In the past few years it has been discovered that certain functions of the innate immune system, which build the first line of defense against pathogenic microorganisms, are altered with aging. Among the cells of the innate immune system, neutrophilic granulocytes (polymorphonuclear leukocytes, PMN, neutrophils) eliminate invaded bacteria and fungi and play an accepted important role in regulation of the immune response. In vitro studies demonstrate that neutrophilic functions such as phagocytosis, generation of reactive oxygen species (ROS), intracellular killing, degranulation, and possibly chemotaxis are changed in elderly persons whereas the number of circulating neutrophils are unaltered compared to young persons. However, the reported data of different investigators regarding the above-mentioned functions are sometimes controversial. This may result from the use of different isolation methods of neutrophils, the degree of contaminating cells and preactivation of neutrophils during isolation. It could be shown that most of the adhesion surface molecules and receptors of neutrophils are not impaired in function and expression with age. But there is increasing evidence that age-related changes affect receptor-dependent signal transduction and membrane content and fluidity, which in turn lead to a decline in function and in inhibition of apoptosis. Further research has to be done to identify the molecular mechanisms that are responsible for the age-related modulations in human neutrophils.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ligthart GJ, Corberand JX, Fournier C et al (1984) Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 28:47–55

    Article  PubMed  CAS  Google Scholar 

  2. Ligthart GJ, Corberand JX, Geertzen HGM et al (1994) Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol. Mech Ageing Dev 55:89–105

    Article  Google Scholar 

  3. Theilgaard-Mönch K, Porse BT, Borregaard N (2006) Systems biology of neutrophil differentiation and immune response. Curr Opin Immunol 18:54–60

    Article  PubMed  CAS  Google Scholar 

  4. Hellewell PG, Williams TJ (1994) The neutrophil. In: Hellewell PG, Williams TJ, (eds) Immunopharmacology of neutrophils. London, Academic Press, pp 1–4

    Google Scholar 

  5. Lee A, Whyte MK, Haslett C (1993) Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 54:283–288

    PubMed  CAS  Google Scholar 

  6. Hannah S, Mecklenburgh K, Rahman I et al (1995) Hypoxia prolongs neutrophil survival in vitro. FEBS Lett 372:233–237

    Article  PubMed  CAS  Google Scholar 

  7. Moulding DA, Quayle JA, Hart CA et al (1998) Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood 92:2495–2502

    PubMed  CAS  Google Scholar 

  8. Chilvers ER, Cadwallader KA, Reed BJ et al (2000) The function and fate of neutrophils at the inflamed site: prospects for therapeutic intervention. J R Coll Physicians Lond 34:68–74

    PubMed  CAS  Google Scholar 

  9. Fulop T Jr (1994) Signal transduction changes in granulocytes and lymphocytes with ageing. Immunol Lett 40:259–268

    Article  PubMed  CAS  Google Scholar 

  10. O’Neill L (2006) How Toll–like receptors signal: what we know and what we don’t know. Curr Opin Immunol 18:3–9

    Article  PubMed  CAS  Google Scholar 

  11. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173–182

    Article  PubMed  CAS  Google Scholar 

  12. Altstaedt J, Kirchner H, Rink L (1996) Cytokine production of neutrophils is limited to interleukin-8. Immunology 89:563–568

    Article  PubMed  CAS  Google Scholar 

  13. Schröder AK, von der Ohe M, Kolling U et al (2006) Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators. Immunology (Epub Jul 25)

    Google Scholar 

  14. Schröder AK, von der Ohe M, Fleischer D et al (2005) Differential synthesis of two interleukin-1 receptor antagonist variants and interleukin-8 by peripheral blood neutrophils. Cytokine 32:246–253

    Article  PubMed  CAS  Google Scholar 

  15. Kolling UK, Hansen F, Braun J et al (2001) Leucocyte response and anti-inflammatory cytokines in community acquired pneumonia. Thorax 56:121–125

    Article  PubMed  CAS  Google Scholar 

  16. Lloyd AR, Oppenheim JJ (1992) Poly’s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol Today 13:169–172

    Article  PubMed  CAS  Google Scholar 

  17. Meyer KC, Rosenthal NS, Soergel P et al (1998) Neutrophils and low grade inflammation in the seemingly normal aging human lung. Mech Ageing Dev 104;169–181

    Article  PubMed  CAS  Google Scholar 

  18. Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

    Article  PubMed  CAS  Google Scholar 

  19. 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–M212

    PubMed  CAS  Google Scholar 

  20. 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 84:113–126

    Article  PubMed  CAS  Google Scholar 

  21. Cakman I, Kirchner H, Rink L (1997) Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons. J.Interferon Cytokine Res 17:469–472

    PubMed  CAS  Google Scholar 

  22. Lord JM, Butcher S, Killampali V et al (2001) Neutrophil ageing and immunesenescence. Mech Ageing Dev 122:1521–1535

    Article  PubMed  CAS  Google Scholar 

  23. Butcher S, Chahel H, Lord JM (2000) Ageing and the neutrophil: no appetite for killing? Immunology 100:411–416

    Article  PubMed  CAS  Google Scholar 

  24. Schröder AK, Rink L (2003) Neutrophil immunity of the elderly. Mech Ageing Dev 124:419–425

    Article  PubMed  CAS  Google Scholar 

  25. Rabatic S, Sabioncello A, Dekaris D et al (1988) Age-related changes in functions of peripheral blood phagocytes. Mech Ageing Dev 45:223–229

    Article  PubMed  CAS  Google Scholar 

  26. Ginaldi L, De Martinis M, D’Ostilio A et al (1999) The Immune system in the elderly I. Specific humoral immunity. Immunol Res 20:101–108

    Article  PubMed  CAS  Google Scholar 

  27. Ginaldi L, De Martinis M, D’Ostilio A et al (1999) The Immune system in the elderly II. Specific cellular immunity. Immunol Res 20:109–115

    Article  PubMed  CAS  Google Scholar 

  28. Ginaldi L, De Martinis M, D’Ostilio A et al (1999) The immune system in the elderly: III. Innate immunity. Immunol Res 20:117–126

    Article  PubMed  CAS  Google Scholar 

  29. Emmanuelli, G, Lanzio, M, Anfossi, T et al (1986) Influence of age on polymorphonuclear leukocytes in vitro: phagocytic activity in healthy human subjects. Gerontology 32:308–316

    Google Scholar 

  30. Mege, JL, Capo, C, Michel, B et al (1988) Phagocytic cell function in aged subjects. Neurobiol Aging 9: 217–220

    Article  PubMed  CAS  Google Scholar 

  31. Esparza B, Sanchez H, Ruiz M et al (1996) Neutrophil function in elderly persons assessed by flow cytometry. Immunol Invest 25:185–190

    Article  PubMed  CAS  Google Scholar 

  32. Wenisch C, Patruta S, Daxbock F et al (2000) Effect of age on human neutrophil function. J Leukoc Biol 67:40–45

    PubMed  CAS  Google Scholar 

  33. Butcher SK, Chahel H, Nayak L et al (2001) Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol 70:881–886

    PubMed  CAS  Google Scholar 

  34. MacGregor RR, Shalit M (1990) Neutrophil function in healthy elderly subjects. J Gerontol 45:M55–M60

    PubMed  CAS  Google Scholar 

  35. Braga PC, Sala MT, Dal Sasso M et al (1998) Age-associated differences in neutrophil oxidative burst (chemiluminescence). Exp Gerontol 33:477–484

    Article  PubMed  CAS  Google Scholar 

  36. Braga PC, Sala MT, Dal Sasso M et al (1998) Influence of age on oxidative bursts (chemiluminescence) of polymorphonuclear neutrophil leukocytes. Gerontology 44:192–197

    Article  PubMed  CAS  Google Scholar 

  37. Biasi D, Carletto A, Dell’Agnola C et al (1996) Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 20:673–681

    Article  PubMed  CAS  Google Scholar 

  38. Tortorella C, Piazzolla G, Spaccavento F et al (2000) Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging. Mech Ageing Dev 119:69–82

    Article  PubMed  CAS  Google Scholar 

  39. Seres I, Csongor J, Mohacsi A et al (1993) Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes. Mech Ageing Dev 71:143–154

    Article  PubMed  CAS  Google Scholar 

  40. Tortorella, C, Polignano, A, Piazzolla, G et al (1996) Lipopolysaccharide-, granulocytemonocyte colony stimulating factor- and pentoxifylline-mediated effects on formyl-methionyl- leucine-phenylalanine-stimuated neutrophil respiratory burst in the elderly. Microbios 85:189–198

    PubMed  CAS  Google Scholar 

  41. Whitelaw DA, Rayner BL, Willcox PA (1992) Community-acquired bacteremia in the elderly: a prospective study of 121 cases. J Am Geriatr Soc 40:996–1000

    PubMed  CAS  Google Scholar 

  42. 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 8:539–546

    Article  CAS  Google Scholar 

  43. Larbi A, Dupuis G, Douziech N et al (2004) Low-grade inflammation with aging has consequences for T-lymphocyte signaling. Ann N Y Acad Sci 1030:125–133

    Article  PubMed  CAS  Google Scholar 

  44. Plackett TP, Boehmer ED, Faunce DE et al (2004) Aging and innate immune cells. J Leukoc 76:291–299

    Article  CAS  Google Scholar 

  45. Piazzolla G, Tortorella C, Serrone M et al (1998) Modulation of cytoskeleton assembly capacity and oxidative response in aged neutrophils. Immunopharmacol Immunotoxicol 20:251–266

    Article  PubMed  CAS  Google Scholar 

  46. Babior BM (1992) Neutrophil function as related to neutrophil–endothelial interactions. Nouv Rev Fr Hematol 34 (Suppl.):829–835

    Google Scholar 

  47. Rossi AG, Hellewell PG (1994) Mechanisms of neutrophil accumulation in tissues. In: Hellewell PG, Williams TJ, (eds) Immunopharmacology of neutrophils. London, Academic Press, pp 223–243

    Google Scholar 

  48. McLaughlin B, O’Malley K, Cotter TG (1986) Age-related differences in granulocytochemotaxis and degranulation. Clin Sci 70:59–62

    PubMed  CAS  Google Scholar 

  49. 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 44:1655–1664

    Article  PubMed  CAS  Google Scholar 

  50. Corberand J, Ngyen F, Laharrague P et al (1981) Polymorphonuclear functions and aging in humans. J Am Geriatr Soc 29;391–397

    PubMed  CAS  Google Scholar 

  51. 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 18:321–329

    Article  PubMed  CAS  Google Scholar 

  52. 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;195–205

    Article  PubMed  CAS  Google Scholar 

  53. Fulop Jr T, Fouquet C, Allaire P et al (1997) Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev 96:15–34

    Article  PubMed  CAS  Google Scholar 

  54. Di Lorenzo G, Balistreri CR, Candore G et al (1999) Granulocyte and natural killer activity in the elderly. Mech Ageing Dev 108:25–38

    Article  PubMed  CAS  Google Scholar 

  55. Fulop Jr T, Larbi A, Linteau A et al (2002) Role of Mcl-1 and Bax expression alterations in the decreased rescue of human neutrophils from apoptosis by GM-CSF with aging. Ann N Y Acad Sci 973: 305–308

    Article  Google Scholar 

  56. Fulop T, Larbi A, Douziech N et al (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell 3:217–226

    Article  PubMed  CAS  Google Scholar 

  57. Varga Z, Kovacs EM, Paragh G et al (1988) Effect of elastin peptides and N-formyl-methionylleucyl phenylalanine on cytosolic free calcium in polymorphonuclear leukocytes of healthy middle-aged and elderly subjects. Clin Biochem 21:127–130

    Article  PubMed  CAS  Google Scholar 

  58. Fulop Jr T, Varga Z, Csongor J et al (1989) Age related impairment in phosphatidylinositol breakdown of polymorphonuclear granulocytes. FEBS Lett 245:249–252

    Article  CAS  Google Scholar 

  59. Lipschitz DA, Udupa KB, Indelicato SR et al (1991) Effect of age on second messenger generation in neutrophils. Blood 78:1347–1354

    PubMed  CAS  Google Scholar 

  60. Mohacsi A, Fulop Jr 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 25:285–288

    Article  PubMed  CAS  Google Scholar 

  61. Klut ME, Ruehlmann DO, Li L et al (2002) Age-related changes in the calcium homeostasis of adherent neutrophils. Exp Gerontol 37:533–541

    Article  PubMed  CAS  Google Scholar 

  62. Fortin CF, Larbi A, Lesur O et al (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 79:1061–1072

    Article  PubMed  CAS  Google Scholar 

  63. Walrand S, Guillet C, Boirie Y et al (2006) Insulin differentially regulates monocyte and polymorphonuclear neutrophil functions in healthy young and elderly humans. J Clin Endocrinol Metab 91:2738–2748

    Article  PubMed  CAS  Google Scholar 

  64. De Martinis M, Modesti M, Ginaldi L (2004) Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol 82:415–420

    Article  PubMed  Google Scholar 

  65. Noble JM, Ford GA, Thomas TH (1999) Effect of aging on CD11b and CD69 surface expression by vesicular insertion in human polymorphonuclear leukocytes. Clin Sci 97:323–329

    Article  PubMed  CAS  Google Scholar 

  66. Solana R, Alonso MC, Pena J (1999) Natural killer cells in healthy aging. Exp Gerontol 34:435–443

    Article  PubMed  CAS  Google Scholar 

  67. Yuli I, Tamonga A, Snyderman R (1982) Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers. Proc Natl Acad Sci U S A 79:5906–5910

    Article  PubMed  CAS  Google Scholar 

  68. Alvarez E, Ruiz-Guttierrez V, Sobrino F et al (2001) Age-related changes in membrane lipid composition, fluidity and respiratory burst in rat peripheral neutrophils. Clin Exp Immunol 124;95–102

    Article  PubMed  CAS  Google Scholar 

  69. Rao KMK, Currie MS, Padmadabhan J et al (1992) Age-related alterations in actin cytoskeleton and receptor expression in human leukocytes. J Gerontol 47:B37–B44

    PubMed  CAS  Google Scholar 

  70. Renshaw M, Rockwell J, Engleman C et al (2002) Cutting edge: impaired Toll-like receptor expression and function in aging. J Immunol 169:4697–4701

    PubMed  CAS  Google Scholar 

  71. Boehmer ED, Goral J, Faunce DE et al (2004) Age dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokines by production and mitogen-activated protein kinase expression. J Leukoc Biol 75:342–349

    Article  PubMed  CAS  Google Scholar 

  72. Gabriel P, Cakman I, Rink L (2002) Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. Exp Gerontol 37:235–247

    Article  PubMed  CAS  Google Scholar 

  73. Ibs KH, Rink L (2001) The immune system in aging. Z Gerontol Geriatr 34:480–485

    Article  PubMed  CAS  Google Scholar 

  74. Fagiolo U, Cossarizza A, Scala E et al (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23:2375–2378

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Immunology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany

    Peter Uciechowski & Lothar Rink

Authors
  1. Peter Uciechowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lothar Rink
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Uciechowski, P., Rink, L. (2009). Neutrophil Granulocyte Functions in the Elderly. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_22

Download citation

Publish with us

Policies and ethics

Search

Navigation