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Caught with their PAMPs down? The extracellular signalling actions of molecular chaperones are not due to microbial contaminants

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Cell Stress and Chaperones Aims and scope

Abstract

In recent years, it has been hypothesised that a new signalling system may exist in vertebrates in which secreted molecular chaperones form a dynamic continuum between the cellular stress response and corresponding homeostatic physiological mechanisms. This hypothesis seems to be supported by the finding that many molecular chaperones are released from cells and act as extracellular signals for a range of cells. However, this nascent field of biological research seems to suffer from an excessive criticism that the biological activities of molecular chaperones are due to undefined components of the microbial expression hosts used to generate recombinant versions of these proteins. In this article, a number of the proponents of the cell signalling actions of molecular chaperones take this criticism head-on. They show that sufficient evidence exists to support fully the hypothesis that molecular chaperones have cell–cell signalling actions that are likely to be part of the homeostatic mechanism of the vertebrate.

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Acknowledgements

BH and ARMC wish to thank the Medical Research Council, Wellcome Trust, British Heart Foundation and Arthritis Research Campaign for funding their studies.

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Authors and Affiliations

  1. Division of Microbial Diseases, UCL-Eastman Dental Institute, University College London, 256 Gray’s Inn Road, London, WC1X 8LD, UK

    Brian Henderson

  2. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    Stuart K. Calderwood

  3. Centre of Infection, Division of Cellular and Molecular Medicine, St. George’s University of London, London, SW17 ORE, UK

    Anthony R. M. Coates

  4. Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Irun Cohen

  5. Institute of Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, 3584CL, Utrecht, The Netherlands

    Willem van Eden

  6. Kings College London at Guy’s Hospital, London, SE1 9RT, UK

    Thomas Lehner

  7. Immunobiology Research Group, The Medical School, University of Sheffield, Sheffield, S10 2RX, UK

    A. Graham Pockley

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  1. Brian Henderson
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  2. Stuart K. Calderwood
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  3. Anthony R. M. Coates
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Correspondence to Brian Henderson.

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Henderson, B., Calderwood, S.K., Coates, A.R.M. et al. Caught with their PAMPs down? The extracellular signalling actions of molecular chaperones are not due to microbial contaminants. Cell Stress and Chaperones 15, 123–141 (2010). https://doi.org/10.1007/s12192-009-0137-6

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  • DOI: https://doi.org/10.1007/s12192-009-0137-6

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