Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages.
Heat shock proteins (hsps) are intracellular chaperones that play a key role in the recovery from stress. Hsp70, the major stress-induced hsp, has been found in the extracellular medium and is capable of activating immune cells. The mechanism involved in Hsp70 release is controversial because this protein does not present a consensual secretory signal. In this study, we have shown that Hsp70 integrates into artificial lipid bilayer openings of ion conductance pathways. In addition, this protein was found inserted into the plasma membrane of cells after stress. Hsp70 was released into the extracellular environment in a membrane-associated form, sharing the characteristics of this protein in the plasma membrane. Extracellular membranes containing Hsp70 were at least 260-fold more effective than free recombinant protein in inducing TNF-alpha production as an indicator of macrophage activation. These observations suggest that Hsp70 translocates into the plasma membrane after stress and is released within membranous structures from intact cells, which could act as a danger signal to activate the immune system.
Vega
Virginia L
VL
Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA.
Rodríguez-Silva
Monica
M
Frey
Tiffany
T
Gehrmann
Mathias
M
Diaz
Juan Carlos
JC
Steinem
Claudia
C
Multhoff
Gabriele
G
Arispe
Nelson
N
De Maio
Antonio
A
D001426:Bacterial Proteins / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008051:Lipid Bilayers / Q000276:immunology / Q000378:metabolism; D008164:Luminescent Proteins / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D017830:Octoxynol / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D012995:Solubility
D001426:Bacterial Proteins; D018840:HSP70 Heat-Shock Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D008164:Luminescent Proteins; D008565:Membrane Proteins; C054562:yellow fluorescent protein, Bacteria; D017830:Octoxynol