In Vivo Tissue Source and Releasing Signal for Endogenous Extracellular Hsp72

  • Monika FleshnerEmail author
  • Thomas Maslanik
  • Lida A. Beninson
Part of the Heat Shock Proteins book series (HESP, volume 5)


Environmental or emotional challenge triggers a cascading series of responses collectively termed the “stress response”. Acute activation of the stress response modulates many aspects of physiology, including the immune system. Hans Seyle, the founding father of the concept of “biologic stress”, proposed in the 1900s that tissues release “alarm signals” in response to local and/or systemic challenge, and that these signals can initiate and direct inflammatory responses. There is a renewed interest in the investigation of tissue alarm signals and such signals have been coined “danger signals”, “DAMPS” (danger associated molecular patterns) and “hidden-self recognition signals”. This chapter focuses on heat shock protein 72 (Hsp72) as one potential alarm signal. Activation of the systemic stress response and the release of norepinephrine from sympathetic nerve terminals, stimulates the release of endogenous Hsp72 into the blood. We hypothesize that the tissue source of in vivo released Hsp72 is the small intestine, and that NE binds to alpha1 adrenergic receptors expressed on intestinal epithelial cells triggering the release of Hsp72 into the blood. Furthermore, we hypothesize that lipopolysaccharide derived from endogenous gut microflora binds Hsp72, and that the extracellular Hsp72-LPS complex may contribute to stress-associated modulation of in vivo inflammatory processes


Danger signals inflammation stress alarm signals bacterial translocation sympathetic nervous system β1-adrenergic receptors 



adrenergic receptors


danger associated molecular patterns


extracellular heat shock proteins


intracellular HSP


major histocompatibility complex




peripheral blood mononuclear cells


toll-like receptors


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Monika Fleshner
    • 1
    Email author
  • Thomas Maslanik
    • 2
  • Lida A. Beninson
    • 2
  1. 1.Department of Integrative PhysiologyUniversity of Colorado-BoulderBoulderUSA
  2. 2.Department of Integrative PhysiologyThe Center for Neuroscience, University of ColoradoBoulderUSA

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