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Review
. 2010 Mar;15(2):123-41.
doi: 10.1007/s12192-009-0137-6.

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

Brian Henderson  1 , Stuart K Calderwood, Anthony R M Coates, Irun Cohen, Willem van Eden, Thomas Lehner, A Graham Pockley
Affiliations
Review

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

Brian Henderson et al. Cell Stress Chaperones. 2010 Mar.

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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Figures

Fig. 1
Fig. 1
The effect of intracellular calcium chelator BAPTA-AM (a) or treatment with proteinase K (b) on the production of TNF-α stimulated by Hsp70, its two fragments or LPS. Suppression of RANTES (CCL-5) production by mAb to CD40 or CD4 in THP1 cells stimulated with Hsp70 (c) or LPS (d)
Fig. 2
Fig. 2
a Identification of a stimulating epitope within peptide 387–426 and inhibiting epitope within peptide 457–496 using DCs co-stimulated with Hsp70 and with two adjacent or overlapping 20-mer peptides. b Stimulating epitope p407–426 at the base of L3, 4 and L4, 5 loops and the suppressive epitope (p457–496) in the β sheet. c Effect of peptides 407–426 and 457–496 on p38 MAP kinase phosphorylation stimulated by Hsp70 or LPS of lysed DCs by enzyme immunoassay or by Western blotting
Fig. 3
Fig. 3
Possible explanations and tests for the cytokine-inducing actions of chaperones, especially if these have been expressed in E. coli
See this image and copyright information in PMC

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