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Release of Heat Shock Proteins: Passive Versus Active Release Mechanisms

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Heat Shock Proteins: Potent Mediators of Inflammation and Immunity

Part of the book series: Heat Shock Proteins ((HESP,volume 1))

Abstract

There is now no doubt that heat shock proteins have a profound immunoregulatory effect on the host’s immune system. This knowledge has successfully been harnessed to generate a number of important clinical trails. However, one intriguing question that remains to be answered is how heat shock proteins (HSP) which do not have peptide leader sequence targeting secretion can gain access to the extracellular milieu. This chapter will discuss the most recent findings in the area of HSP release and attempts to broadly categorize these findings into two basic mechanisms; the passive and active mechanisms

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References

  • Adewoye, A. H., Klings, E. S., Farber, H. W., Palaima, E., Bausero, M. A., McMahon, L., Odhiambo, A., Surinder, S., Yoder, M., Steinberg, M. H. and Asea, A. (2005) Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70. Am J Hematol 78, 240–2.

    PubMed  CAS  Google Scholar 

  • Adewoye, A. H. and McMahon, L. (2005) Chaperones and disease. N Engl J Med 353, 2821–2; author reply 2821–2.

    Google Scholar 

  • Asano, M., Toda, M., Sakaguchi, N. and Sakaguchi, S. (1996) Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 184, 387–96.

    PubMed  CAS  Google Scholar 

  • Asea, A. (2003) Chaperokine-induced signal transduction pathways. Exerc. Immunol. Rev. 9, 25–33.

    PubMed  Google Scholar 

  • Asea, A. (2005) Stress proteins and initiation of immune response: chaperokine activity of hsp72. Exerc. Immunol. Rev. 11, 34–45.

    PubMed  Google Scholar 

  • Asea, A., Kabingu, E., Stevenson, M. A. and Calderwood, S. K. (2000a) HSP70 peptide-bearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones 5, 425–31.

    CAS  Google Scholar 

  • Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W., Koo, G. C. and Calderwood, S. K. (2000b) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6, 435–42.

    CAS  Google Scholar 

  • Asea, A., Rehli, M., Kabingu, E., Boch, J. A., Bare, O., Auron, P. E., Stevenson, M. A. and Calderwood, S. K. (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277, 15028–34.

    PubMed  CAS  Google Scholar 

  • Ausiello, C. M., Palazzo, R., Spensieri, F., Fedele, G., Lande, R., Ciervo, A., Fioroni, G. and Cassone, A. (2005) 60-kDa heat shock protein of Chlamydia pneumoniae is a target of T-cell immune response. J Biol Regul Homeost Agents 19, 136–40.

    PubMed  CAS  Google Scholar 

  • Banfi, G., Malavazos, A., Iorio, E., Dolci, A., Doneda, L., Verna, R. and Corsi, M. M. (2006) Plasma oxidative stress biomarkers, nitric oxide and heat shock protein 70 in trained elite soccer players. Eur J Appl Physiol 96, 483–6.

    PubMed  CAS  Google Scholar 

  • Barreto, A., Gonzalez, J. M., Kabingu, E., Asea, A. and Fiorentino, S. (2003) Stress-induced release of HSC70 from human tumors. Cell. Immunol. 222, 97–104.

    PubMed  CAS  Google Scholar 

  • 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, 1539–46.

    PubMed  CAS  Google Scholar 

  • Basu, S. and Srivastava, P. K. (2000) Heat shock proteins: the fountainhead of innate and adaptive immune responses. Cell Stress Chaperones 5, 443–51.

    PubMed  CAS  Google Scholar 

  • Bausero, M. A., Gastpar, R., Multhoff, G. and Asea, A. (2005) Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72. J Immunol 175, 2900–12.

    PubMed  CAS  Google Scholar 

  • Bergmeier, L. A. and Lehner, T. (2006) Innate and adaptive mucosal immunity in protection against HIV infection. Adv Dent Res 19, 21–8.

    PubMed  CAS  Google Scholar 

  • Binder, C. J., Chang, M. K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A. and Witztum, J. L. (2002) Innate and acquired immunity in atherogenesis. Nat Med 8, 1218–26.

    PubMed  CAS  Google Scholar 

  • Binder, R. J., Anderson, K. M., Basu, S. and Srivastava, P. K. (2000) Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo. J Immunol 165, 6029–35.

    PubMed  CAS  Google Scholar 

  • Bosco, N., Hung, H. C., Pasqual, N., Jouvin-Marche, E., Marche, P. N., Gascoigne, N. R. and Ceredig, R. (2006) Role of the T cell receptor alpha chain in the development and phenotype of naturally arising CD4+CD25+ T cells. Mol Immunol 43, 246–54.

    PubMed  CAS  Google Scholar 

  • Brinkmann, M. M. and Schulz, T. F. (2006) Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J Gen Virol 87, 1047–74.

    PubMed  CAS  Google Scholar 

  • 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, 21601–6.

    PubMed  CAS  Google Scholar 

  • Campisi, J., Leem, T. H., Greenwood, B. N., Hansen, M. K., Moraska, A., Higgins, K., Smith, T. P. and Fleshner, M. (2003) Habitual physical activity facilitates stress-induced HSP72 induction in brain, peripheral, and immune tissues. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R520–30.

    PubMed  CAS  Google Scholar 

  • Chandawarkar, R. Y., Wagh, M. S., Kovalchin, J. T. and Srivastava, P. (2004) Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis. Int Immunol 16, 615–24.

    PubMed  CAS  Google Scholar 

  • 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, 3631–8.

    PubMed  CAS  Google Scholar 

  • Cohen-Sfady, M., Nussbaum, G., Pevsner-Fischer, M., Mor, F., Carmi, P., Zanin-Zhorov, A., Lider, O. and Cohen, I. R. (2005) Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway. J Immunol 175, 3594–602.

    PubMed  CAS  Google Scholar 

  • Dolnikov, A., Shen, S., Passioura, T. and Symonds, G. (2003) Bone marrow reconstitution as a relevant model of genetically programmed leukemia. Curr Med Chem Cardiovasc Hematol Agents 1, 83–97.

    PubMed  CAS  Google Scholar 

  • Dybdahl, B., Wahba, A., Haaverstad, R., Kirkeby-Garstad, I., Kierulf, P., Espevik, T. and Sundan, A. (2004) On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein 70 is released after on-pump surgery. Eur J Cardiothorac Surg 25, 985–92.

    PubMed  Google Scholar 

  • Dybdahl, B., Wahba, A., Lien, E., Flo, T. H., Waage, A., Qureshi, N., Sellevold, O. F., Espevik, T. and Sundan, A. (2002) Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation 105, 685–90.

    PubMed  CAS  Google Scholar 

  • Escola, J. M., Kleijmeer, M. J., Stoorvogel, W., Griffith, J. M., Yoshie, O. and Geuze, H. J. (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273, 20121–7.

    PubMed  CAS  Google Scholar 

  • Facciponte, J. G., MacDonald, I. J., Wang, X. Y., Kim, H., Manjili, M. H. and Subjeck, J. R. (2005) Heat shock proteins and scavenger receptors: role in adaptive immune responses. Immunol Invest 34, 325–42.

    PubMed  CAS  Google Scholar 

  • Facciponte, J. G., Wang, X. Y., Macdonald, I. J., Park, J. E., Arnouk, H., Grimm, M. J., Li, Y., Kim, H., Manjili, M. H., Easton, D. P. and Subjeck, J. R. (2006) Heat shock proteins HSP70 and GP96: structural insights. Cancer Immunol Immunother 55, 339–46.

    PubMed  CAS  Google Scholar 

  • 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, 957–62.

    PubMed  CAS  Google Scholar 

  • Fischetti, V. A. (2005) Bacteriophage lytic enzymes: novel anti-infectives. Trends Microbiol 13, 491–6.

    PubMed  CAS  Google Scholar 

  • Fleshner, M., Campisi, J., Amiri, L. and Diamond, D. M. (2004) Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones. Psychoneuroendocrinology 29, 1142–52.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Fleshner, M. and Johnson, J. D. (2005) Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperthermia 21, 457–71.

    PubMed  CAS  Google Scholar 

  • Fontenot, J. D., Dooley, J. L., Farr, A. G. and Rudensky, A. Y. (2005a) Developmental regulation of Foxp3 expression during ontogeny. J Exp Med 202, 901–6.

    CAS  Google Scholar 

  • Fontenot, J. D., Rasmussen, J. P., Gavin, M. A. and Rudensky, A. Y. (2005b) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6, 1142–51.

    CAS  Google Scholar 

  • Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G. and Rudensky, A. Y. (2005c) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22, 329–41.

    CAS  Google Scholar 

  • Fontenot, J. D. and Rudensky, A. Y. (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6, 331–7.

    PubMed  CAS  Google Scholar 

  • Fukudo, S., Abe, K., Hongo, M., Utsumi, A. and Itoyama, Y. (1995) Psychophysiological stress induces heat shock cognate protein (HSC) 70 mRNA in the cerebral cortex and stomach of rats. Brain Res 675, 98–102.

    PubMed  CAS  Google Scholar 

  • Fukudo, S., Abe, K., Hongo, M., Utsumi, A. and Itoyama, Y. (1997) Brain-gut induction of heat shock protein (HSP) 70 mRNA by psychophysiological stress in rats. Brain Res 757, 146–8.

    PubMed  CAS  Google Scholar 

  • Fukudo, S., Abe, K., Itoyama, Y., Mochizuki, S., Sawai, T. and Hongo, M. (1999) Psychophysiological stress induces heat shock cognate protein 70 messenger RNA in the hippocampus of rats. Neuroscience 91, 1205–8.

    PubMed  CAS  Google Scholar 

  • Fukudo, S., Nomura, T., Muranaka, M. and Taguchi, F. (1993) Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study. J Clin Gastroenterol 17, 133–41.

    PubMed  CAS  Google Scholar 

  • Galazka, G., Stasiolek, M., Walczak, A., Jurewicz, A., Zylicz, A., Brosnan, C. F., Raine, C. S. and Selmaj, K. W. (2006) Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis. J Immunol 176, 1588–99.

    PubMed  CAS  Google Scholar 

  • Ganter, M. T., Ware, L. B., Howard, M., Roux, J., Gartland, B., Matthay, M. A., Fleshner, M. and Pittet, J. F. (2006) Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury. Am J Physiol Lung Cell Mol Physiol 291, L354–61.

    PubMed  CAS  Google Scholar 

  • Gastpar, R., Gehrmann, M., Bausero, M. A., Asea, A., Gross, C., Schroeder, J. A. and Multhoff, G. (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65, 5238–47.

    PubMed  CAS  Google Scholar 

  • Gavin, M. A., Clarke, S. R., Negrou, E., Gallegos, A. and Rudensky, A. (2002) Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat Immunol 3, 33–41.

    PubMed  CAS  Google Scholar 

  • Gazda, L. S., Smith, T., Watkins, L. R., Maier, S. F. and Fleshner, M. (2003) Stressor exposure produces long-term reductions in antigen-specific T and B cell responses. Stress 6, 259–67.

    PubMed  CAS  Google Scholar 

  • Gross, C., Hansch, D., Gastpar, R. and Multhoff, G. (2003a) Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol Chem 384, 267–79.

    CAS  Google Scholar 

  • Gross, C., Koelch, W., DeMaio, A., Arispe, N. and Multhoff, G. (2003b) Cell surface-bound heat shock protein 70 (Hsp70) mediates perforin-independent apoptosis by specific binding and uptake of granzyme B. J Biol Chem 278, 41173–81.

    CAS  Google Scholar 

  • Gross, C., Schmidt-Wolf, I. G., Nagaraj, S., Gastpar, R., Ellwart, J., Kunz-Schughart, L. A. and Multhoff, G. (2003c) Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells. Cell Stress Chaperones 8, 348–60.

    CAS  Google Scholar 

  • Gruenberg, J. and van der Goot, F. G. (2006) Mechanisms of pathogen entry through the endosomal compartments. Nat Rev Mol Cell Biol 7, 495–504.

    PubMed  CAS  Google Scholar 

  • Guech-Ongey, M., Brenner, H., Twardella, D. and Rothenbacher, D. (2006) Chlamydia pneumoniae, heat shock proteins 60 and risk of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes: a prospective study. BMC Cardiovasc Disord 6, 17.

    PubMed  Google Scholar 

  • Guzhova, I., Kislyakova, K., Moskaliova, O., Fridlanskaya, I., Tytell, M., Cheetham, M. and Margulis, B. (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res. 914, 66–73.

    PubMed  CAS  Google Scholar 

  • Hammerman, S. I., Klings, E. S., Hendra, K. P., Upchurch, G. R., Jr., Rishikof, D. C., Loscalzo, J. and Farber, H. W. (1999) Endothelial cell nitric oxide production in acute chest syndrome. Am J Physiol 277, H1579–92.

    PubMed  CAS  Google Scholar 

  • Hansson, G. K. and Libby, P. (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6, 508–19.

    PubMed  CAS  Google Scholar 

  • Hightower, L. E. and Guidon, P. T., Jr. (1989) Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins. J Cell Physiol 138, 257–66.

    PubMed  CAS  Google Scholar 

  • Hori, S., Nomura, T. and Sakaguchi, S. (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–61.

    PubMed  CAS  Google Scholar 

  • Hoshida, S., Nishino, M., Tanouchi, J., Kishimoto, T. and Yamada, Y. (2005) Acute Chlamydia pneumoniae infection with heat-shock-protein-60-related response in patients with acute coronary syndrome. Atherosclerosis 183, 109–12.

    PubMed  CAS  Google Scholar 

  • 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, 511–7.

    PubMed  CAS  Google Scholar 

  • Johnson, J. D., Campisi, J., Sharkey, C. M., Kennedy, S. L., Nickerson, M. and Fleshner, M. (2005a) Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72. J Appl Physiol 99, 1789–95.

    CAS  Google Scholar 

  • Johnson, J. D., Campisi, J., Sharkey, C. M., Kennedy, S. L., Nickerson, M., Greenwood, B. N. and Fleshner, M. (2005b) Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience 135, 1295–307.

    CAS  Google Scholar 

  • Johnson, J. D. and Fleshner, M. (2006) Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72. J Leukoc Biol 79, 425–34.

    PubMed  CAS  Google Scholar 

  • Jonsdottir, I. H., Asea, A., Hoffmann, P., Dahlgren, U. I., Andersson, B., Hellstrand, K. and Thoren, P. (1996a) Voluntary chronic exercise augments in vivo natural immunity in rats. J Appl Physiol 80, 1799–803.

    CAS  Google Scholar 

  • Jonsdottir, I. H., Asea, A., Hoffmann, P., Hellstrand, K. and Thoren, P. (1996b) Natural immunity and chronic exercise in rats. The involvement of the spleen and the splenic nerves. Life Sci 58, 2137–46.

    CAS  Google Scholar 

  • Jonsdottir, I. H., Johansson, C., Asea, A., Johansson, P., Hellstrand, K., Thoren, P. and Hoffmann, P. (1997) Duration and mechanisms of the increased natural cytotoxicity seen after chronic voluntary exercise in rats. Acta Physiol Scand 160, 333–9.

    PubMed  CAS  Google Scholar 

  • Kasow, K. A., Chen, X., Knowles, J., Wichlan, D., Handgretinger, R. and Riberdy, J. M. (2004) Human CD4+CD25+ regulatory T cells share equally complex and comparable repertoires with CD4+CD25- counterparts. J Immunol 172, 6123–8.

    PubMed  CAS  Google Scholar 

  • Klings, E. S. and Farber, H. W. (2001) Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease. Respir Res 2, 280–5.

    PubMed  CAS  Google Scholar 

  • Lancaster, G. I. and Febbraio, M. A. (2005) Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem 280, 23349–55.

    PubMed  CAS  Google Scholar 

  • Land, W. G. (2005) The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation. Transplantation 79, 505–14.

    PubMed  Google Scholar 

  • Lehner, T. and Anton, P. A. (2002) Mucosal immunity and vaccination against HIV. Aids 16 Suppl 4, S125–32.

    PubMed  Google Scholar 

  • Lehner, T., Bergmeier, L. A., Wang, Y., Tao, L., Sing, M., Spallek, R. and van der Zee, R. (2000) Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity. Eur J Immunol 30, 594–603.

    PubMed  CAS  Google Scholar 

  • Lehner, T. and Shearer, G. M. (2002) Alternative HIV vaccine strategies. Science 297, 1276–7.

    PubMed  CAS  Google Scholar 

  • Lewthwaite, J., Owen, N., Coates, A., Henderson, B. and Steptoe, A. (2002) Circulating human heat shock protein 60 in the plasma of British civil servants: relationship to physiological and psychosocial stress. Circulation 106, 196–201.

    PubMed  CAS  Google Scholar 

  • Mathis, J. M., Stoff-Khalili, M. A. and Curiel, D. T. (2005) Oncolytic adenoviruses–selective retargeting to tumor cells. Oncogene 24, 7775–91.

    PubMed  CAS  Google Scholar 

  • Melcher, A., Todryk, S., Hardwick, N., Ford, M., Jacobson, M. and Vile, R. G. (1998) Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med 4, 581–7.

    PubMed  CAS  Google Scholar 

  • Mizoguchi, K., Kunishita, T., Chui, D. H. and Tabira, T. (1992) Stress induces neuronal death in the hippocampus of castrated rats. Neurosci Lett 138, 157–60.

    PubMed  CAS  Google Scholar 

  • Moehler, M., Zeidler, M., Schede, J., Rommelaere, J., Galle, P. R., Cornelis, J. J. and Heike, M. (2003) Oncolytic parvovirus H1 induces release of heat-shock protein HSP72 in susceptible human tumor cells but may not affect primary immune cells. Cancer Gene Ther 10, 477–80.

    PubMed  CAS  Google Scholar 

  • Moehler, M. H., Zeidler, M., Wilsberg, V., Cornelis, J. J., Woelfel, T., Rommelaere, J., Galle, P. R. and Heike, M. (2005) Parvovirus H-1-induced tumor cell death enhances human immune response in vitro via increased phagocytosis, maturation, and cross-presentation by dendritic cells. Hum Gene Ther 16, 996–1005.

    PubMed  CAS  Google Scholar 

  • Moser, C., Schmidbauer, C., Gurtler, U., Gross, C., Gehrmann, M., Thonigs, G., Pfister, K. and Multhoff, G. (2002) Inhibition of tumor growth in mice with severe combined immunodeficiency is mediated by heat shock protein 70 (Hsp70)-peptide-activated, CD94 positive natural killer cells. Cell Stress Chaperones 7, 365–73.

    PubMed  CAS  Google Scholar 

  • Multhoff, G., Pfister, K., Gehrmann, M., Hantschel, M., Gross, C., Hafner, M. and Hiddemann, W. (2001) A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity. Cell Stress Chaperones 6, 337–44.

    PubMed  CAS  Google Scholar 

  • Nickerson, M., Elphick, G. F., Campisi, J., Greenwood, B. N. and Fleshner, M. (2005) Physical activity alters the brain Hsp72 and IL-1beta responses to peripheral E. coli challenge. Am J Physiol Regul Integr Comp Physiol 289, R1665–74.

    PubMed  CAS  Google Scholar 

  • Noessner, E., Gastpar, R., Milani, V., Brandl, A., Hutzler, P. J., Kuppner, M. C., Roos, M., Kremmer, E., Asea, A., Calderwood, S. K. and Issels, R. D. (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol 169, 5424–32.

    PubMed  CAS  Google Scholar 

  • Nomura, T. and Sakaguchi, S. (2005) Naturally arising CD25+CD4+ regulatory T cells in tumor immunity. Curr Top Microbiol Immunol 293, 287–302.

    PubMed  CAS  Google Scholar 

  • O’Shea, C. C. (2005) Viruses: tools for tumor target discovery, and agents for oncolytic therapies – an introduction. Oncogene 24, 7636–9.

    PubMed  CAS  Google Scholar 

  • O’Shea, C. C., Soria, C., Bagus, B. and McCormick, F. (2005) Heat shock phenocopies E1B-55K late functions and selectively sensitizes refractory tumor cells to ONYX-015 oncolytic viral therapy. Cancer Cell 8, 61–74.

    PubMed  CAS  Google Scholar 

  • Panjwani, N. N., Popova, L. and Srivastava, P. K. (2002) Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J. Immunol. 168, 2997–3003.

    PubMed  CAS  Google Scholar 

  • Pittet, J. F., Lee, H., Morabito, D., Howard, M. B., Welch, W. J. and Mackersie, R. C. (2002) Serum levels of Hsp 72 measured early after trauma correlate with survival. J Trauma 52, 611–7; discussion 617.

    Google Scholar 

  • Prohaszka, Z., Singh, M., Nagy, K., Kiss, E., Lakos, G., Duba, J. and Fust, G. (2002) Heat shock protein 70 is a potent activator of the human complement system. Cell Stress Chaperones 7, 17–22.

    PubMed  CAS  Google Scholar 

  • Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J. and Geuze, H. J. (1996) B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183, 1161–72.

    PubMed  CAS  Google Scholar 

  • Rose, N. R. (2000) Viral damage or ’molecular mimicry’-placing the blame in myocarditis. Nat Med 6, 631–2.

    PubMed  CAS  Google Scholar 

  • Rose, N. R. and Mackay, I. R. (2000) Molecular mimicry: a critical look at exemplary instances in human diseases. Cell Mol Life Sci 57, 542–51.

    PubMed  CAS  Google Scholar 

  • Sakaguchi, S. (2004) Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22, 531–62.

    PubMed  CAS  Google Scholar 

  • Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. and Toda, M. (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155, 1151–64.

    PubMed  CAS  Google Scholar 

  • Sakaguchi, S., Takahashi, T. and Nishizuka, Y. (1982a) Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis. J Exp Med 156, 1577–86.

    CAS  Google Scholar 

  • Sakaguchi, S., Takahashi, T. and Nishizuka, Y. (1982b) Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer. J Exp Med 156, 1565–76.

    CAS  Google Scholar 

  • Sakaguchi, S., Toda, M., Asano, M., Itoh, M., Morse, S. S. and Sakaguchi, N. (1996) T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases. J Autoimmun 9, 211–20.

    PubMed  CAS  Google Scholar 

  • 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, 239–46.

    PubMed  CAS  Google Scholar 

  • Schneider, E. M., Niess, A. M., Lorenz, I., Northoff, H. and Fehrenbach, E. (2002) Inducible hsp70 expression analysis after heat and physical exercise: transcriptional, protein expression, and subcellular localization. Ann N Y Acad Sci 973, 8–12.

    PubMed  CAS  Google Scholar 

  • SenGupta, D., Norris, P. J., Suscovich, T. J., Hassan-Zahraee, M., Moffett, H. F., Trocha, A., Draenert, R., Goulder, P. J., Binder, R. J., Levey, D. L., Walker, B. D., Srivastava, P. K. and Brander, C. (2004) Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II. J Immunol 173, 1987–93.

    PubMed  CAS  Google Scholar 

  • Singh-Jasuja, H., Scherer, H. U., Hilf, N., Arnold-Schild, D., Rammensee, H. G., Toes, R. E. and Schild, H. (2000a) The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. Eur. J. Immunol. 30, 2211–5.

    CAS  Google Scholar 

  • Singh-Jasuja, H., Toes, R. E., Spee, P., Munz, C., Hilf, N., Schoenberger, S. P., Ricciardi-Castagnoli, P., Neefjes, J., Rammensee, H. G., Arnold-Schild, D. and Schild, H. (2000b) Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis. J. Exp. Med. 191, 1965–74.

    CAS  Google Scholar 

  • Son, Y. S., Park, J. H., Kang, Y. K., Park, J. S., Choi, H. S., Lim, J. Y., Lee, J. E., Lee, J. B., Ko, M. S., Kim, Y. S., Ko, J. H., Yoon, H. S., Lee, K. W., Seong, R. H., Moon, S. Y., Ryu, C. J. and Hong, H. J. (2005) Heat shock 70-kDa protein 8 isoform 1 is expressed on the surface of human embryonic stem cells and downregulated upon differentiation. Stem Cells 23, 1502–13.

    PubMed  CAS  Google Scholar 

  • Soti, C., Nagy, E., Giricz, Z., Vigh, L., Csermely, P. and Ferdinandy, P. (2005) Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146, 769–80.

    PubMed  CAS  Google Scholar 

  • Srivastava, P. (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20, 395–425.

    PubMed  CAS  Google Scholar 

  • Srivastava, P. K. (2000) Heat shock protein-based novel immunotherapies. Drug News Perspect 13, 517–22.

    PubMed  CAS  Google Scholar 

  • Srivastava, P. K. (2005) Immunotherapy for human cancer using heat shock protein-Peptide complexes. Curr Oncol Rep 7, 104–8.

    PubMed  CAS  Google Scholar 

  • Steensberg, A., Dalsgaard, M. K., Secher, N. H. and Pedersen, B. K. (2006) Cerebrospinal fluid IL-6, HSP72, and TNF-alpha in exercising humans. Brain Behav Immun Apr 26; [Epub ahead of print].

    Google Scholar 

  • Steinberg, M. H. and Adewoye, A. H. (2006) Modifier genes and sickle cell anemia. Curr Opin Hematol 13, 131–6.

    PubMed  CAS  Google Scholar 

  • Suri-Payer, E., Amar, A. Z., Thornton, A. M. and Shevach, E. M. (1998) CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol 160, 1212–8.

    PubMed  CAS  Google Scholar 

  • Thorne, S. H., Bartlett, D. L. and Kirn, D. H. (2005a) The use of oncolytic vaccinia viruses in the treatment of cancer: a new role for an old ally? Curr Gene Ther 5, 429–43.

    CAS  Google Scholar 

  • Thorne, S. H., Hermiston, T. and Kirn, D. (2005b) Oncolytic virotherapy: approaches to tumor targeting and enhancing antitumor effects. Semin Oncol 32, 537–48.

    CAS  Google Scholar 

  • Thornton, A. M. and Shevach, E. M. (1998) CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 188, 287–96.

    PubMed  CAS  Google Scholar 

  • Tytell, M. and Hooper, P. L. (2001) Heat shock proteins: new keys to the development of cytoprotective therapies. Expert Opin Ther Targets 5, 267–87.

    PubMed  CAS  Google Scholar 

  • van Eden, W. (2006) Immunoregulation of autoimmune diseases. Hum Immunol 67, 446–53.

    PubMed  Google Scholar 

  • van Eden, W., Hauet-Broere, F., Berlo, S., Paul, L., van der Zee, R., de Kleer, I., Prakken, B. and Taams, L. (2005a) Stress proteins as inducers and targets of regulatory T cells in arthritis. Int Rev Immunol 24, 181–97.

    Google Scholar 

  • van Eden, W., Holoshitz, J., Nevo, Z., Frenkel, A., Klajman, A. and Cohen, I. R. (1985) Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans. Proc Natl Acad Sci U S A 82, 5117–20.

    PubMed  Google Scholar 

  • van Eden, W., van der Zee, R. and Prakken, B. (2005b) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5, 318–30.

    Google Scholar 

  • van Eden, W., Wendling, U., Paul, L., Prakken, B., van Kooten, P. and van der Zee, R. (2000) Arthritis protective regulatory potential of self-heat shock protein cross-reactive T cells. Cell Stress Chaperones 5, 452–7.

    PubMed  Google Scholar 

  • Wang, Y., Kelly, C. G., Singh, M., McGowan, E. G., Carrara, A. S., Bergmeier, L. A. and Lehner, T. (2002) Stimulation of Th1-polarizing cytokines, C-C chemokines, maturation of dendritic cells, and adjuvant function by the peptide binding fragment of heat shock protein 70. J Immunol 169, 2422–9.

    PubMed  CAS  Google Scholar 

  • Wheeler, D. S., Fisher, L. E., Jr., Catravas, J. D., Jacobs, B. R., Carcillo, J. A. and Wong, H. R. (2005) Extracellular hsp70 levels in children with septic shock. Pediatr Crit Care Med 6, 308–11.

    PubMed  Google Scholar 

  • Whittall, T., Wang, Y., Kelly, C. G., Thompson, R., Sanderson, J., Lomer, M., Soon, S. Y., Bergmeier, L. A., Singh, M. and Lehner, T. (2006a) Tumour necrosis factor-alpha production stimulated by heat shock protein 70 and its inhibition in circulating dendritic cells and cells eluted from mucosal tissues in Crohn’s disease. Clin Exp Immunol 143, 550–9.

    CAS  Google Scholar 

  • Whittall, T., Wang, Y., Younson, J., Kelly, C., Bergmeier, L., Peters, B., Singh, M. and Lehner, T. (2006b) Interaction between the CCR5 chemokine receptors and microbial HSP70. Eur J Immunol.

    Google Scholar 

  • Wick, G., Kleindienst, R., Schett, G., Amberger, A. and Xu, Q. (1995a) Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis. Int Arch Allergy Immunol 107, 130–1.

    CAS  Google Scholar 

  • Wick, G., Schett, G., Amberger, A., Kleindienst, R. and Xu, Q. (1995b) Is atherosclerosis an immunologically mediated disease? Immunol Today 16, 27–33.

    CAS  Google Scholar 

  • Wing, K., Fehervari, Z. and Sakaguchi, S. (2006) Emerging possibilities in the development and function of regulatory T cells. Int Immunol 18, 991–1000.

    PubMed  CAS  Google Scholar 

  • Yokota, S., Minota, S. and Fujii, N. (2006) Anti-HSP auto-antibodies enhance HSP-induced pro-inflammatory cytokine production in human monocytic cells via Toll-like receptors. Int Immunol 18, 573–80.

    PubMed  CAS  Google Scholar 

  • Zanin-Zhorov, A., Bruck, R., Tal, G., Oren, S., Aeed, H., Hershkoviz, R., Cohen, I. R. and Lider, O. (2005a) Heat shock protein 60 inhibits Th1-mediated hepatitis model via innate regulation of Th1/Th2 transcription factors and cytokines. J Immunol 174, 3227–36.

    CAS  Google Scholar 

  • Zanin-Zhorov, A., Tal, G., Shivtiel, S., Cohen, M., Lapidot, T., Nussbaum, G., Margalit, R., Cohen, I. R. and Lider, O. (2005b) Heat shock protein 60 activates cytokine-associated negative regulator suppressor of cytokine signaling 3 in T cells: effects on signaling, chemotaxis, and inflammation. J Immunol 175, 276–85.

    CAS  Google Scholar 

  • Zitvogel, L., Fernandez, N., Lozier, A., Wolfers, J., Regnault, A., Raposo, G. and Amigorena, S. (1999) Dendritic cells or their exosomes are effective biotherapies of cancer. Eur. J. Cancer 35 Suppl 3, S36–8.

    PubMed  CAS  Google Scholar 

  • Zitvogel, L., Regnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., Ricciardi-Castagnoli, P., Raposo, G. and Amigorena, S. (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med. 4, 594–600.

    PubMed  CAS  Google Scholar 

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  1. Division of Investigative Pathology, Scott & White Memorial Hospital and Clinic and The Texas A&M University System Health Science Center College of Medicine, Temple, Texas, USA

    Alexzander A.A. Asea

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  1. Effie and Wofford Cain Centennial Endowed Chair in Clinical Pathology, Chief, Division of Investigative Pathology Scott & White Memorial Hospital and Clinic and The Texas A&M University System Health Science Center College of Medicine Temple, TX, U.S.A

    Alexzander A. A. Asea

  2. Department of Surgery, School of Medicine, University of California, San Diego, CA, U.S.A

    Antonio De Maio

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Asea, A.A. (2007). Release of Heat Shock Proteins: Passive Versus Active Release Mechanisms. In: Asea, A.A., Maio, A.D. (eds) Heat Shock Proteins: Potent Mediators of Inflammation and Immunity. Heat Shock Proteins, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-5585-0_1

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