Exogenous mammalian extracellular HSP70 reduces endotoxin manifestations at the cellular and organism levels.
In this study, we checked whether HSP70 preparations of different origins are able to protect model animals (rats) from endotoxic shock and modify the response of myeloid cells to lipopolysaccharide (LPS) challenge. It was shown that HSP70 preparations can effectively protect organisms from endotoxic shock by strongly decreasing mortality and restoring both homeostasis and various hemodynamic characteristics. At the cellular level, HSP70 preparations significantly inhibit LPS-induced reactive oxygen species production in various myeloid cells and decrease NO expression in macrophages, which is enhanced after LPS priming. In parallel, HSP70 preconditioning partially normalizes neutrophil apoptosis, which is disturbed as a result of LPS stimulation. These results suggest that the antiseptic actions of HSP70 preparations are probably realized at the level of receptor membrane complexes of myeloid cells, which represent the major target of LPS action. Taken together, our findings show that extracellular mammalian HSP70 may play an important role in innate immunity modulation and stimulation of endogenous protective mechanisms, both at the cellular and organism levels, which make this protein a promising base for the development of efficient antiseptic drugs.
Engelhardt Institute of Molecular Biology of the Russian Academy of Science, Vavilova, Moscow, Russia.
Elena
E
Rozhkova
Marina
M
Yurinskaya
Olga
O
Zatsepina
David
D
Garbuz
Vadim
V
Karpov
Sergei
S
Surkov
Arkady
A
Murashev
Vladimir
V
Ostrov
Boris
B
Margulis
Mikhail
M
Evgen'ev
Maxim
M
Vinokurov
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002477:Cells / Q000276:immunology / Q000378:metabolism*; D004731:Endotoxins / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D008322:Mammals / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology*
D004731:Endotoxins; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species