title: Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis.
abstract: BACKGROUND
  It is not well understood whether the process of autophagy is accelerated or blocked in sepsis, and whether it is beneficial or harmful to the immune defense mechanism over a time course during sepsis. Our aim was to determine both the kinetics and the role of autophagy in sepsis.
  
  
  METHODS
  We examined autophagosome and autolysosome formation in a cecal ligation and puncture (CLP) mouse model of sepsis (in C57BL/6N mice and GFP-LC3 transgenic mice), using western blotting, immunofluorescence, and electron microscopy. We also investigated the effect of chloroquine inhibition of autophagy on these processes.
  
  
  RESULTS
  Autophagy, as demonstrated by increased LC3-II/LC3-I ratios, is induced in the liver, heart, and spleen over 24 h after CLP. In the liver, autophagosome formation peaks at 6 h and declines by 24 h. Immunofluorescent localization of GFP-LC3 dots (alone and with lysosome-associated membrane protein type 1 (LAMP1)), as well as electron microscopic examination, demonstrate that both autophagosomes and autolysosomes are increased after CLP, suggesting that intact autophagy mechanisms operate in the liver in this model. Furthermore, inhibition of autophagy process by chloroquine administration immediately after CLP resulted in elevated serum transaminase levels and a significant increase in mortality.
  
  
  CONCLUSIONS
  All autophagy-related processes are properly activated in the liver in a mouse model of sepsis; autophagy appears to play a protective role in septic animals.
authors.forename: Waka
authors.initials: W
authors.lastname: Takahashi
authors.forename: Eizo
authors.initials: E
authors.lastname: Watanabe
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.forename: Haruko
authors.initials: H
authors.lastname: Watanabe-Takano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshidome
authors.forename: Paul E
authors.initials: PE
authors.lastname: Swanson
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Shigeto
authors.initials: S
authors.lastname: Oda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002432:Cecum / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011677:Punctures / Q000009:adverse effects; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*