Microcirculatory alterations of hepatic and mesenteric microcirculation in endotoxin tolerance.
LPSs getting access to the circulation of mammalian organisms cause typical systemic inflammatory reactions with symptoms characteristic for acute sepsis. One possibility to attenuate LPS effects is to expose a host to a challenge with low LPS doses, which results in the establishment of "endotoxin tolerance" (ET). Because the microcirculation is of particular importance in LPS action, it seemed of interest to analyze leukocyte-endothelial interactions in the mesentery and liver once endotoxin tolerance has been established and are challenged with LPS. The mesenteric and hepatic microcirculation was investigated by intravital microscopy. After induction of ET LPS, shock was induced by i.v. injection of LPS, and microcirculation of the mesentery and liver was examined. Endotoxin tolerance resulted in reduced ex vivo TNF-alpha synthesis of whole blood. In vivo LPS caused no increase of body temperature. In sinusoids, LPS challenge increased adherence of leukocytes in naive rats, which was almost completely prevented by ET induction. In contrast, in postsinusoidal venules, leukocyte adherence was more intense after ET induction and subsequent to LPS application. Similarly, in postcapillary mesenteric venules, increased adherence of leukocytes after LPS challenge in the ET group was observed. After LPS injection, the endothelial barrier was more disturbed in the nontolerant group when compared with the ET group. Soluble L-selectin and intercellular adhesion molecule were elevated in both ET and untreated rats. Endotoxin tolerance influences leukocyte-endothelial interaction differentially depending on organ and vessel area.
Lendemans
Sven
S
Department of Trauma Surgery, Unit of Surgical Research, University Hospital of Duisburg-Essen, Germany. sven.lendemans@gmx.de
Peszko
Adam
A
Oberbeck
Reiner
R
Schmitz
Daniel
D
Husain
Baher
B
Burkhard
Marcus
M
Schade
Fritz Ulrich
FU
Flohe
Sascha
S
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D019040:E-Selectin / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019040:E-Selectin; D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin