Exogenous heat shock protein 70 mediates sepsis manifestations and decreases the mortality rate in rats.
Mammalian responses to bacterial lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria can lead to an uncontrolled inflammatory reaction that can be deadly for the host. We checked whether heat shock protein 70 (Hsp70) protein is able to protect animals from the deleterious effects of bacterial LPS by monitoring the effect of exogenous Hsp70 injections before and after LPS administration. Our research with rats demonstrates for the first time that administration of exogeneous Hsp70 before and after LPS challenges can reduce mortality rates and modify several parameters of hemostasis and hemodynamics. Hsp70 isolated from bovine muscles showed significant protective effects against the impaired coagulation and fibrinolytic systems caused by LPS, and reduced the mortality caused by Escherichia coli and Salmonella typhimurium LPS injections significantly. Characteristically, Hsp70 preparations used in the experiments result in different effects when administered before and after an LPS challenge, and the effects of Hsp70 injections also differ significantly depending on the origin of the LPS (E coli vs S typhimurium). Based on our data, mammalian Hsp70 appears to be an attractive target in therapeutic strategies designed to stimulate endogenous protective mechanisms against many deleterious consequences of septic shock by accelerating the functional recovery of susceptible organs in humans.
Kustanova
Gul'sara A
GA
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Murashev
Arcady N
AN
Karpov
Vadim L
VL
Margulis
Boris A
BA
Guzhova
Irina V
IV
Prokhorenko
Izabella R
IR
Grachev
Sergei V
SV
Evgen'ev
Michael B
MB
D000818:Animals; D002417:Cattle; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000401:mortality*; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012481:Salmonella Infections, Animal / Q000401:mortality*; D012486:Salmonella typhimurium / Q000472:pathogenicity; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D016019:Survival Analysis; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides