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Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects

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Cell Stress and Chaperones Aims and scope

Abstract

Open heart surgery is a unique model to study the interplay between cellular injury, regulation of inflammatory responses and tissue repair. Stress-inducible heat shock protein 70-kDa (Hsp70) provides a molecular link between these events. In addition to molecular chaperoning, Hsp70 exerts modulatory effects on endothelial cells and leukocytes involved in inflammatory networks. Hsp70 residing in the intracellular compartment is part of an inhibitory feedback loop that acts on nuclear factor kappaB (NF-κB). In contrast, extracellular Hsp70 is recognized by multiple germline-encoded immune receptors, e.g., Toll-like receptor (TLR) 2, TLR4, LOX-1, CD91, CD94, CCR5 and CD40. Hsp70 is thereby able to enhance chemotaxis, phagocytosis and cytolytic activity of innate immune cells and stimulate antigen-specific responses. These apparent contradictory pro- and anti-inflammatory effects of endogenous Hsp70 in the context of cardiac surgery are still not fully understood. An all-embracing model of the compartmentalized effects of endogenous Hsp70 in the orchestration of inflammatory responses in cardiac surgery is proposed.

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Abbreviations

ACC:

aortic cross-clamping

APC:

antigen-presenting cells

CPB:

cardiopulmonary bypass

HSP:

heat shock proteins

IL-1:

interleukin-1

IFN-γ:

interferon-gamma

MHC:

major histocompatibility complex

NF-κB:

nuclear factor kappa B

SIRS:

systemic inflammatory response syndrome

TGF-β:

transforming growth factor-beta

TLR:

toll-like receptor

TNF-α:

tumor necrosis factor-alpha

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Acknowledgements

B.J.P. is supported by Grants from the Dutch Organization for Scientific Research (NWO VIDI innovation grant), the 5th European Framework Grant ‘hsp for therapy’ and the Dutch Arthritis Foundation.

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  1. Department of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Home mailbox KC.03.063.0, PO Box 85090, 3508 AB, Utrecht, The Netherlands

    Petrus R. de Jong, Alvin W. L. Schadenberg & Berent J. Prakken

  2. Department of Pediatric Intensive Care, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands

    Alvin W. L. Schadenberg & Nicolaas J. G. Jansen

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de Jong, P.R., Schadenberg, A.W.L., Jansen, N.J.G. et al. Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects. Cell Stress and Chaperones 14, 117–131 (2009). https://doi.org/10.1007/s12192-008-0066-9

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