Role of LPS in the hepatic microvascular dysfunction elicited by cecal ligation and puncture in mice.
OBJECTIVE
Sepsis remains a leading cause of death in critically ill patients. Because endotoxemia is viewed as a key mediator of sepsis-induced inflammation, administration of bacterial endotoxin (LPS) is often used to simulate sepsis in experimental animals. This study tests the hypothesis that LPS is a critical determinant of the hepatic microvascular dysfunction in mice made septic by cecal ligation and puncture (CLP).


METHODS
Intravital videomicroscopy was used to quantify sinusoidal perfusion, and platelet and leukocyte adhesion in terminal hepatic venules (THV) and sinusoids in LPS-sensitive and LPS-insensitive mice subjected to CLP or LPS (i.p.). mRNA expression of TLR-2, TLR-4, MyD-88, and Ly-96 was also assessed.


RESULTS
While LPS-sensitive mice responded to both CLP and LPS challenges with elevated leukocyte and platelet adhesion in THV and sinusoids, and a reduced sinusoidal perfusion density, LPS-insensitive mice exhibited comparable blood cell adhesion and sinusoidal malperfusion following CLP, but not LPS. Hepatic mRNA of MyD-88 and TLR-2 was elevated in the CLP and LPS groups. Endotoxin was not detectable in the blood of LPS-sensitive mice after CLP, but was elevated after LPS administration.


CONCLUSIONS
These findings do not support a major role for LPS in the hepatic microvascular disturbances associated with polymicrobial sepsis.
Singer
Georg
G
Department of Pediatric Surgery, Medical University of Graz, Austria.
Houghton
Jeff
J
Rivera
Chantal A
CA
Anthoni
Christoph
C
Granger
D N
DN
D000818:Animals; D001792:Blood Platelets / Q000166:cytology; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D007962:Leukocytes / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008102:Liver Circulation / Q000187:drug effects*; D008107:Liver Diseases / Q000209:etiology* / Q000382:microbiology; D051379:Mice; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D018715:Microscopy, Video; D018805:Sepsis / Q000209:etiology*
D004731:Endotoxins; D008070:Lipopolysaccharides