European Journal of Applied Physiology

, Volume 98, Issue 3, pp 250–255 | Cite as

Role of Hsp72 and norepinephrine in the moderate exercise-induced stimulation of neutrophils’ microbicide capacity

  • E. OrtegaEmail author
  • E. Giraldo
  • M. D. Hinchado
  • M. Martínez
  • S. Ibáñez
  • A. Cidoncha
  • M. E. Collazos
  • J. J. García
Original Article


The influence of a single session of moderate exercise (45 min at 55% of VO2 max) performed by young sedentary men (23–25 years old) on the microbicidal capacity of neutrophils was compared by using both direct (killing of phagocytosed Candida albicans) and indirect (superoxide anion production measured by NBT reduction) techniques. In addition, the role of norepinephrine and heat shock protein (Hsp) 72 in the modulation of microbicide capacity of neutrophils was evaluated during the protocol of exercise and recovery period (24 h). No significant changes were found in the superoxide production after exercise. However, immediately after exercise there was an increase in the destruction of C. albicans, which remained higher than basal values 1 day later. This behaviour was similar to the changes found in the serum extracellular Hsp72 concentrations (an increase after exercise that remained higher than basal values 24 h later). In vitro, the raised physiological concentration of Hsp72 after exercise also increased the microbicide capacity of neutrophils with respect to controls and the values induced by the basal concentration of the protein. This indicates that Hsp72 is participating as a “stress mediator” of the stimulated microbicide activity during moderate exercise. However, norepinephrine is not mediating the increased killing of C. albicans during exercise.


Exercise Stress Immunology Neutrophils Hsp72 Norepinephrine 



This investigation is supported by grants from Consejería de Sanidad y Consumo (SCSS04) and Consejería de Educación, Ciencia y Tecnología (2PR04A076) of the Junta de Extremadura and Fondo Social Europeo.


  1. Asea A (2005) Stress proteins and initiation of immune response: chaperokine activity of Hsp72. Exerc Immunol Rev 11:34–45PubMedGoogle Scholar
  2. Asea A, Kraef SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood ST (2000) Hsp70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442PubMedCrossRefGoogle Scholar
  3. Asea A, Rehlis M, Kabingu E, Boch JA, Baré O, Auron P, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70. Role of Toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034PubMedCrossRefGoogle Scholar
  4. Campisi J, Leem TH, Greenwood BN, Hansen MK, Moraska A, Higgins K, Smith TP, Fleshner M (2003a) Habitual physical activity facilitates stress-induced HSP72 induction in brain, peripheral, and immune tissues. Am J Physiol Regul Integr Comp Physiol 284:R520–R530Google Scholar
  5. Campisi J, Leem TH, Fleshner M (2003b) Stress-induced extracellular Hsp72 is a functionally significant danger signal to the immune system. Cell Stress Chaperones 8:372–286CrossRefGoogle Scholar
  6. Fehrenbach E, Niess AM, Voelker K, Northoff H, Mooren FC (2005) Exercise intensity and duration affect blood soluble HSP72. Int J Sports Med 26:552–557PubMedCrossRefGoogle Scholar
  7. Fleshner M, Johnson JD (2005) Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperth 21:457–471CrossRefGoogle Scholar
  8. Fleshner M, Campisi J, Johnson JD (2003) Can exercise stress facilitate innate immunity? A functional role for stress-induced extracellular Hsp72. Exerc Immunol Rev 9:6–23PubMedGoogle Scholar
  9. Gabriel HH, Kindermann W (1998) Adhesion molecules during immune response to exercise. Can J Physiol Pharmacol 76:512–523PubMedCrossRefGoogle Scholar
  10. Hennigan SM, Wang JH, Redmond HP, Bouchier-Hayves D (1999) Neutrophil heat shock protein expression and activation correlate with increased apoptosis following transmigration through the endothelial barrier. Shock 12:32–38PubMedCrossRefGoogle Scholar
  11. Johnson JD, Campisi J, Sharkey CM, Kennedy SL, Nickerson M, Fleshner M (2005) Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72. J Appl Physiol 99:1789–1795PubMedCrossRefGoogle Scholar
  12. Kurt-Jones EA, Mandell L, Whitney C, Padgett A, Gosselin K, Newburger PE, Finber RW (2002) Role of Toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR-2 mediated interleukin 8 responses in neutrophils. Blood 100:1860–1868PubMedGoogle Scholar
  13. Macha M, Schlafer M, Kluger MJ (1990) Human neutrophil hydrogen peroxide generation following physical exercise. J Sports Med Phys Fit 30:412–419Google Scholar
  14. Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305PubMedCrossRefGoogle Scholar
  15. Niess AM, Dickhuth H, Northoff H, Fehrenbach E (1999) Free radicals and oxidative stress in exercise-immunological aspects. Exerc Immunol Rev 5:22–56PubMedGoogle Scholar
  16. Ortega E (1994) Influence of exercise on phagocytosis. Int J Sports Med 15:S172–S178Google Scholar
  17. Ortega E (2003) Neuroendocrine mediators in the modulation of phagocytosis by exercise: physiological implications. Exerc Immunol Rev 9:70–93PubMedGoogle Scholar
  18. Ortega E, Collazos ME, Maynar M, Barriga C, De la Fuente M (1993) Stimulation of the phagocytic function of neutrophils in sedentary men after acute moderate exercise. Eur J Appl Physiol 66:60–64CrossRefGoogle Scholar
  19. Ortega E, Marchena JM, García JJ, Barriga C, Rodríguez AB (2005a) Norepinephrine as mediator in the stimulation of phagocytosis induced by moderate exercise. Eur J Appl Physiol 93:714–718CrossRefGoogle Scholar
  20. Ortega E, García JJ, Marchena JM, Barriga C, Rodríguez AB (2005b) Phagocytes may counteract the “open window” situation during a bout of moderate exercise performed by sedentary individuals: role of noradrenaline. J Appl Biomed 3:75–82Google Scholar
  21. Peake JM (2002) Exercise-induced alterations in neutrophil degranulation and respiratory burst activity: possible mechanisms of action. Exerc Immunol Rev 8:49–100PubMedGoogle Scholar
  22. Power PC, Wang HJ, Manning B, Kell MR, Aherne NF, Wu DQ, Redmond PH (2004) Bacterial lipoprotein delays apoptosis in human neutrophils through inhibition of caspase-3 activity: regulatory roles of CD14 and TLR-2. J Immunol 173:5229–5237PubMedGoogle Scholar
  23. Pyne DB, Baker JA, Smith JA, Telford RD, Weiderman MJ (1996) Exercise and the neutrophil oxidative burst: biological and experimental variability. Eur J Appl Physiol 74:564–571CrossRefGoogle Scholar
  24. Pyne DB, Smith JA, Baker JA, Telford RD, Weiderman MJ (2000) Neutrophil oxidative activity is differentially affected by exercise intensity and type. J Sci Med Sport 3:44–54PubMedCrossRefGoogle Scholar
  25. Robson PJ, Blanin AK, Walsh NP, Castell LM, Gleeson M (1999) Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med 20:128–135PubMedCrossRefGoogle Scholar
  26. Scharhag J, Meyer T, Gabriel HH, Schlick B, Faude O, Kinderman W (2005) Does prolonged cycling of moderate intensity affect immune cell function? Br J Sports Med 39:171–177PubMedCrossRefGoogle Scholar
  27. Smith JA, Pyne DB (1997) Exercise, training, and neutrophil function. Exerc Immunol Rev 3:96–117PubMedGoogle Scholar
  28. Smith JA, Telford RD, Mason IB, Widermann MJ (1990) Exercise, training and neutrophil microbicidal activity. Int J Sports Med 11:179–187PubMedCrossRefGoogle Scholar
  29. Suzuki K, Sato H, Kikuchi T, Abe T, Nakaji S, Sugawara K, Totsuka M, Sato K, Yamaya K (1996) Capacity of circulating neutrophils to produce reactive oxygen species after exhaustive exercise. J Appl Physiol 81:1213–1222PubMedGoogle Scholar
  30. Wallin RP, Lundqvist A, More SH, von Bonin A, Kiessling R, Ljunggren HG (2002) Heat-shock proteins as activators of the innate immune system. Trends Immunol 23:130–135PubMedCrossRefGoogle Scholar
  31. Walsh RC, Koukoulas I, Garnham A, Moseley PL, Hargreaves M, Febbraio MA (2001) Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 6:386–393PubMedCrossRefGoogle Scholar
  32. Wang R, Kovalchin JT, Muhlenkamp P, Chandawarkar RY (2006) Exogenous heat shock protein 70 binds macrophage lipid raft presentation of antigens. Blood 107:1636–1642PubMedCrossRefGoogle Scholar
  33. Zhen L, He M, Long M, Blomgran R, Stendahl O (2004) Pathogen-induced apoptotic neutrophils express heat shock proteins and elicit activation of human macrophages. J Immunol 173:6319–6326Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • E. Ortega
    • 1
    Email author
  • E. Giraldo
    • 1
  • M. D. Hinchado
    • 1
  • M. Martínez
    • 1
  • S. Ibáñez
    • 2
  • A. Cidoncha
    • 3
  • M. E. Collazos
    • 1
  • J. J. García
    • 1
  1. 1.Department of Physiology, Faculty of SciencesUniversity of ExtremaduraBadajozSpain
  2. 2.Faculty of Sport SciencesUniversity of ExtremaduraCáceresSpain
  3. 3.Hospital of D. Benito-VillanuevaBadajozSpain

Personalised recommendations