Mini Review

Cell Stress and Chaperones

, Volume 15, Issue 2, pp 123-141

First online:

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

  • Brian HendersonAffiliated withDivision of Microbial Diseases, UCL-Eastman Dental Institute, University College London Email author 
  • , Stuart K. CalderwoodAffiliated withDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School
  • , Anthony R. M. CoatesAffiliated withCentre of Infection, Division of Cellular and Molecular Medicine, St. George’s University of London
  • , Irun CohenAffiliated withDepartment of Immunology, The Weizmann Institute of Science
  • , Willem van EdenAffiliated withInstitute of Infectious Diseases and Immunology, Utrecht University
  • , Thomas LehnerAffiliated withKings College London at Guy’s Hospital
  • , A. Graham PockleyAffiliated withImmunobiology Research Group, The Medical School, University of Sheffield

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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.


Heat shock proteins Endotoxin Innate immunity Adaptive immunity Inflammation Immunoregulation