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Exercise Intensity and Duration Affect Blood-Soluble HSP72

  • Kishiko Ogawa
  • Elvira FehrenbachEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 5)

Abstract

Extracellular Hsp72 (eHsp72) is elevated during and after acute bouts of exercise. Concentrations of eHsp72 in plasma or serum are dependent on the duration and intensity of exercise. Active secretory processes rather than passive release due to cell damage are considered to function in the exercise-induced release of eHsp72. Up-regulation of eHsp72 in the circulation following acute exercise may contribute to improved immune function; eHsp72 increases stress resistance after binding to stress sensitive recipients, signals tissue destruction and danger to inflammatory cells, and aids in immunosurveillance by transporting intracellular peptides to distant immune cells. It is uncertain whether this exercise-mediated mechanism for eHsp72-regulated activation of the immune system helps to prevent immunologic diseases

Keywords

Exercise acute response immune system blood extracellular heat shock protein 72 

Abbreviations

APC

antigen-presenting cells

ATP

adenosine triphosphate

CCRS

chemokine receptors

eHsp72

extracellular Hsp72

HSP

heat shock proteins

Hsp72

seventy two kilo-dalton HSP

MHC

major histocompatibility complex

PBMC

peripheral blood mononuclear cells

TLR

toll-like receptor

References

  1. Asea, A., Kabingu, E., Stevenson, M. A. and Calderwood, S. K. (2000) HSP70 peptidembearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones. 5, 425–431.CrossRefPubMedGoogle Scholar
  2. Asea, A. (2003) Chaperokine-induced signal transduction pathways. Exerc Immunol Rev. 9, 25–33.PubMedGoogle Scholar
  3. Asea, A. (2005) Stress proteins and initiation of immune response: chaperokine activity of hsp72. Exerc Immunol Rev. 11, 34–45.PubMedGoogle Scholar
  4. Banfi, G., Malavazos, A., Iorio, E., Dolci, A., Doneda, L., Verna, R. and Corsi, M. M. (2005) Plasma oxidative stress biomarkers, nitric oxide and heat shock protein 70 in trained elite soccer players. Eur J Appl Physiol. 96(5), 483–486.CrossRefPubMedGoogle Scholar
  5. Basu, S., Binder, R. J., Suto, R., Anderson, K. M. and Srivastava, P. K. (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol. 12, 1539–1546.CrossRefPubMedGoogle Scholar
  6. Blanchard, N., Lankar, D., Faure, F., Regnault, A., Dumont, C., Raposo, G. and Hivroz, C. (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol. 168(7), 3235–3241.PubMedGoogle Scholar
  7. Broquet, A. H., Thomas, G., Masliah, J., Trugnan, G. and Bachelet, M. (2003) Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J Biol Chem. 278(24), 21601–21606.CrossRefPubMedGoogle Scholar
  8. Calderwood, S. K., Mambula, S. S., Gray, P. J., Jr. and Theriault, J. R. (2007) Extracellular heat shock proteins in cell signaling. FEBS Lett. 581(19), 3689–3694.CrossRefPubMedGoogle Scholar
  9. Campisi, J., Leem, T. H. and Fleshner, M. (2003) Stress-induced extracellular Hsp72 is a functionally significant danger signal to the immune system. Cell Stress Chaperones. 8, 272–286.CrossRefPubMedGoogle Scholar
  10. Clayton, A., Turkes, A., Navabi, H., Mason, M. D. and Tabi, Z. (2005) Induction of heat shock proteins in B-cell exosomes. J Cell Sci. 118(Pt 16), 3631–3638.CrossRefPubMedGoogle Scholar
  11. Daniels, G. A., Sanchez-Perez, L., Diaz, R. M., Kottke, T., Thompson, J., Lai, M., Gough, M., Karim, M., Bushell, A., Chong, H., Melcher, A., Harrington, K. and Vile, R. G. (2004) A simple method to cure established tumors by inflammatory killing of normal cells. Nat Biotechnol. 22(9), 1125–1132.CrossRefPubMedGoogle Scholar
  12. Delneste, Y., Magistrelli, G., Gauchat, J., Haeuw, J., Aubry, J., Nakamura, K., Kawakami-Honda, N., Goetsch, L., Sawamura, T., Bonnefoy, J. and Jeannin, P. (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity. 17(3), 353–362.CrossRefPubMedGoogle Scholar
  13. Di Girolamo, M., Dani, N., Stilla, A., Corda, D. (2005) Physiological relevance of the endogenous mono(ADP-ribosyl)ation of cellular proteins. FEBS J. 272(18), 4565–4575.CrossRefPubMedGoogle Scholar
  14. Doody, A. D., Kovalchin, J. T., Mihalyo, M. A., Hagymasi, A. T., Drake, C. G. and Adler, A. J. (2004) Glycoprotein 96 can chaperone both MHC class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8+ T cell effector function. J Immunol. 172, 6087–6092.PubMedGoogle Scholar
  15. Febbraio, M. A., Ott, P., Nielsen, H. B., Steensberg, A., Keller, C., Krustrup, P., Secher, N. H. and Pedersen, B. K. (2002) Exercise induces hepatosplanchnic release of heat shock protein 72 in humans. J Physiol. 544, 957–962.CrossRefPubMedGoogle Scholar
  16. Febbraio, M. A., Mesa, J. L., Chung, J., Steensberg, A., Keller, C., Nielsen, H. B., Krustrup, P., Ott, P., Secher, N. H. and Pedersen, B. K. (2004) Glucose ingestion attenuates the exercise-induced increase in circulating heat shock protein 72 and heat shock protein 60 in humans. Cell Stress Chaperones. 9(4), 390–396.CrossRefPubMedGoogle Scholar
  17. Fehrenbach, E., Niess, A. M., Schlotz, E., Passek, F., Dickhuth, H. -H. and Northoff, H. (2000a) Transcriptional and translational regulation of heat shock proteins (HSP27, HSP70) in leukocytes of endurance runners. J Appl Physiol. 89, 704–710.PubMedGoogle Scholar
  18. Fehrenbach, E., Passek, F., Niess, A. M., Pohla, H., Weinstock, C., Dickhuth, H.-H. and Northoff, H. (2000b) HSP expression in human leucocytes is modulated by endurance exercise. Med Sci Sports Exerc. 32, 592–600.CrossRefPubMedGoogle Scholar
  19. Fehrenbach, E., Niess, A. M., Dickhuth, H.-H. and Northoff, H. (2002) Influence of exercise, heat and hypoxia on plasma-HSP72. Eur J Physiol (Pfluegers Arch). 443(Suppl.), S362.CrossRefGoogle Scholar
  20. Fehrenbach, E.Cellular responses to environmental stress. In: Molecular and Cellular Exercise Physiology, F. C. Mooren and K. Voelker, eds., Human Kinetics, Muenster, 2005, pp. 199–218.Google Scholar
  21. Fehrenbach, E., Niess, A. M., Voelker, K., Northoff, H. and Mooren, F. C. (2005) Exercise intensity and duration affect blood soluble HSP72. Int J Sports Med. 26, 552–557.CrossRefPubMedGoogle Scholar
  22. Fischer, C. P., Hiscock, N. J., Basu, S., Vessby, B., Kallner, A., Sjöberg, L. B., Febbraio, M. A. and Pedersen, B. K. (2006) Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans. J Appl Physiol. 100(5), 1679–1687.CrossRefPubMedGoogle Scholar
  23. Fleshner, M., Campisi, J. and Johnson, J. D. (2003) Can exercise stress facilitate innate immunity? A functional role for stress-induced extracellular Hsp72. Exerc Immunol Rev. 9, 6–24.PubMedGoogle Scholar
  24. Fleshner, M. and Johnson, J. D. (2005) Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperthermia. 21, 457–471.CrossRefPubMedGoogle Scholar
  25. Floto, R. A., MacAry, P. A., Boname, J. M., Mien, T. S., Kampmann, B., Hair, J. R., Huey, O. S., Houben, E. N., Pieters, J., Day, C., Oehlmann, W., Singh, M., Smith, K. G. and Lehner, P. J. (2006) Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5. Science. 314(5798), 454–458.CrossRefPubMedGoogle Scholar
  26. Gastpar, R., Gross, C., Rossbacher, L., Ellwart, J., Riegger, J., Multhoff, G. (2004) The cell surface-localized heat shock protein 70 epitope TKD induces migration and cytolytic activity selectively in human NK cells. J Immunol. 172(2), 972–980.PubMedGoogle Scholar
  27. Gomez-Merino, D., Drogou, C., Guezennec, C. Y., Burnat, P., Bourrilhon, C., Tomaszewski, A., Milhau, S. and Chennaoui, M. (2006) Comparison of systemic cytokine responses after a long distance triathlon and a 100-km run: relationship to metabolic and inflammatory processes. Eur Cytokine Netw. 17(2), 117–124.PubMedGoogle Scholar
  28. Gu, B. J., Zhang, W. Y., Bendall, L. J., Chessell, I. P., Buell, G. N. and Wiley, J. S. (2000) Expression of P2X(7) purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X(7) receptors. Am J Physiol Cell Physiol. 279(4), C1189–C1197.PubMedGoogle Scholar
  29. Hirose, L., Nosaka, K., Newton, M., Laveder, A., Kano, M., Peake, J. and Suzuki, K. (2004) Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc Immunol Rev. 10, 75–90.PubMedGoogle Scholar
  30. Horn, P., Kalz, A., Lim, C. L., Pyne, D., Saunders, P., Mackinnon, L., Peake, J. and Suzuki, K. (2007) Exercise-recruited NK cells display exercise-associated eHSP-70. Exerc Immunol Rev. 13, 100–111.PubMedGoogle Scholar
  31. Hunter-Lavin, C., Davies, E. L., Bacelar, M. M., Marshall, M. J., Andrew, S. M. and Williams, J. H. (2004) Hsp70 release from peripheral blood mononuclear cells. Biochem Biophys Res Commun. 324, 511–517.CrossRefPubMedGoogle Scholar
  32. Jiang, L. H., Mackenzie, A. B., North, R. A. and Surprenant, A. (2000) Brilliant blue G selectively blocks ATP-gated rat P2X(7) receptors. Mol Pharmacol. 58(1), 82–88.PubMedGoogle Scholar
  33. Johnson, J. D., Campisi, J., Sharkey, C. M., Kennedy, S. L., Nickerson, M. and Fleshner, M. (2005) Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72. J Appl Physiol. 99(5), 1789–1795.CrossRefPubMedGoogle Scholar
  34. Kregel, K. C. and Moseley, P. L. (1996) Differential effects of exercise and heat stress on liver HSP70 accumulation with aging. J Appl Physiol. 80, 547–551.PubMedGoogle Scholar
  35. Lancaster, G. I., Moller, K., Nielsen, B., Secher, N. H., Febbraio, M. A. and Nybo, L. (2004) Exercise induces the release of heat shock protein 72 from the human brain in vivo. Cell Stress Chaperones. 9, 276–280.CrossRefPubMedGoogle Scholar
  36. Lancaster, G. I. and Febbraio, M. A. (2005a) Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem. 280, 23349–23355.CrossRefPubMedGoogle Scholar
  37. Lancaster, G. I. and Febbraio, M. A. (2005b) Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72. Exerc Immunol Rev. 11, 46–52.PubMedGoogle Scholar
  38. Lovell, R., Madden, L., Carroll, S., McNaughton, L. (2007) The time-profile of the PBMC HSP70 response to in vitro heat shock appears temperature-dependent. Amino Acids. 33(1), 137–144.CrossRefPubMedGoogle Scholar
  39. Mambula, S. S. and Calderwood, S. K. (2006) Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J Immunol. 177(11), 7849–7857.PubMedGoogle Scholar
  40. Mambula, S. S., Stevenson, M. A., Ogawa, K. and Calderwood, S. K. (2007) Mechanisms for Hsp70 secretion: crossing membranes without a leader. Methods. 43(3), 168–175.CrossRefPubMedGoogle Scholar
  41. Marshall, H. C., Ferguson, R. A. and Nimmo, M. A. (2006) Human resting extracellular heat shock protein 72 concentration decreases during the initial adaptation to exercise in a hot, humid environment. Cell Stress Chaperones. 11(2), 129–134.CrossRefPubMedGoogle Scholar
  42. Matzinger, P. (2002) An innate sense of danger. Ann N Y Acad Sci. 961, 341–342.CrossRefPubMedGoogle Scholar
  43. Millar, D. G., Garza, K. M., Odermatt, B., Elford, A. R., Ono, N., Li, Z. and Ohashi, P. S. (2003) Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo. Nat Med. 9(12), 1469–1476.CrossRefPubMedGoogle Scholar
  44. Moseley, P. (2000) Stress proteins and the immune response. Immunopharmacology. 48, 299–302.CrossRefPubMedGoogle Scholar
  45. Multhoff, G. (2002) Activation of natural killer cells by heat shock protein 70. Int J Hyperthermia. 18(6), 576–585.CrossRefPubMedGoogle Scholar
  46. Niess, A. M., Fehrenbach, E., Schlotz, E., Sommer, M., Angres, C., Tschositsch, K., Battenfeld, N., Golly, I. C., Biesalski, H. K., Northoff, H. and Dickhuth, H. H. (2002) Effects of RRR-alpha-tocopherol on leukocyte expression of HSP72 in response to exhaustive treadmill exercise. Int J Sports Med. 23(6), 445–452.CrossRefPubMedGoogle Scholar
  47. North, R. A. (2002) Molecular physiology of P2X receptors. Physiol Rev. 82(4), 1013–1067.PubMedGoogle Scholar
  48. Pannicke, T., Fischer, W., Biedermann, B., Schädlich, H., Grosche, J., Faude, F., Wiedemann, P., Allgaier, C., Illes, P., Burnstock, G. and Reichenbach, A. (2000) P2X7 receptors in Müller glial cells from the human retina. J Neurosci. 20(16), 5965–5972.PubMedGoogle Scholar
  49. Peake, J. M., Suzuki, K., Hordern, M., Wilson, G., Nosaka, K. and Coombes, J. S. (2005) Plasma cytokine changes in relation to exercise intensity and muscle damage. Eur J Appl Physiol. 95, 514–521.CrossRefPubMedGoogle Scholar
  50. Pockley, A. G. (2001) Heat shock proteins in health and disease: therapeutic targets or therapeutic agents? Expert Rev Mol Med. 3(23), 1–21.CrossRefPubMedGoogle Scholar
  51. Radons, J. and Multhoff, G. (2005) Immunostimulatory functions of membrane-bound and exported heat shock protein 70. Exerc Immunol Rev. 11, 17–33.PubMedGoogle Scholar
  52. Salo, D. C., Donovan, C. M. and Davies, K. J. (1991) HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. Free Radic Biol Med. 11, 239–246.CrossRefPubMedGoogle Scholar
  53. Schild, H. and Rammensee, H. G. (2000) gp96-the immune system’s Swiss army knife. Nat Immunol. 1(2), 100–101.CrossRefPubMedGoogle Scholar
  54. Segura, E., Amigorena, S. and Théry, C. (2005) Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol Dis. 35(2), 89–93.CrossRefPubMedGoogle Scholar
  55. Skokos, D., Botros, H. G., Demeure, C., Morin, J., Peronet, R., Birkenmeier, G., Boudaly, S. and Mécheri, S. (2003) Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol. 170(6), 3037–3045.PubMedGoogle Scholar
  56. Thériault, J. R., Mambula, S. S., Sawamura, T., Stevenson, M. A. and Calderwood, S. K. (2005) Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells. FEBS Lett. 579(9), 951–1960.CrossRefGoogle Scholar
  57. Vabulas, R. M., Ahmad-Nejad, P., da Costa, C., Miethke, T., Kirschning, C. J., Hacker, H. and Wagner, H. (2001) Endocytosed HSP60 s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem. 276, 31332–31339.CrossRefPubMedGoogle Scholar
  58. van Niel, G., Raposo, G., Candalh, C., Boussac, M., Hershberg, R, Cerf-Bensussan N, Heyman M. (2001) Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology. 121(2), 337–349.CrossRefPubMedGoogle Scholar
  59. Walsh, R. C., Koukoulas, I., Garnham, A., Moseley, P. L., Hargreaves, M. and Febbraio, M. A. (2001) Exercise increases serum Hsp72 in humans. Cell Stress Chaperones. 6, 386–393.CrossRefPubMedGoogle Scholar
  60. Whitham, M., Walker, G. J. and Bishop, N. C. (2006) Effect of caffeine supplementation on the extracellular heat shock protein 72 response to exercise. J Appl Physiol. 101(4), 1222–1227.CrossRefPubMedGoogle Scholar
  61. Yamada, P. M., Amorim, F. T., Moseley, P., Robergs, R. and Schneider, S. M. (2007) Effect of heat acclimation on heat shock protein 72 and interleukin-10 in humans. J Appl Physiol. 103(4), 1196–1204.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Research Team for Social Participation and Health PromotionTokyo Metropolitan Institute of GerontologyTokyoJapan
  2. 2.Institute of Clinical and Experimental Transfusion Medicine (IKET)University of TuebingenTuebingenGermany

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