Alpha-1 acid glycoprotein reduces hepatic leukocyte recruitment in murine models of either early endotoxemia or early sepsis.
OBJECTIVE
To characterize the effect of systemically administered AGP on early leukocyte recruitment in the livers of endotoxemic or septic mice and to determine whether this is influenced by LPS sequestration.


METHODS
Endotoxemia was induced in C57Bl/6 mice via intraperitoneal injection of LPS. Sepsis was induced in mice by cecal ligation and perforation. AGP (165 mg/kg) or saline (20 mL/kg) or HAS (200 mg/kg) was administered immediately after surgery or LPS injection and the hepatic microcirculation was examined by intravital microscopy at four hour.


RESULTS
Leukocyte adhesion in the PSV was reduced by treatment with AGP in mice subjected to either LPS or CLP protocols compared to either saline or HAS treatment. AGP-treated mice also had significantly higher sinusoidal flow in both models. Pre-incubation of LPS with AGP reduced the ability of LPS to recruit leukocytes to the liver microcirculation.


CONCLUSIONS
AGP was more effective in limiting hepatic inflammation and maintaining perfusion than saline or HAS, in both endotoxemic and septic mice. AGP sequestration of LPS may contribute to its anti-inflammatory effects.
Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Canadian Blood Services Research and Development, Hamilton, Ontario, Canada.
Teresa R
TR
McCurdy
Amanda L
AL
Patrick
Louise J
LJ
Eltringham-Smith
Varsha
V
Bhakta
William P
WP
Sheffield
Alison E
AE
Fox-Robichaud
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008833:Microcirculation / Q000187:drug effects*; D009961:Orosomucoid / Q000378:metabolism / Q000494:pharmacology*
D008070:Lipopolysaccharides; D009961:Orosomucoid
alpha-1 acid glycoprotein; cecal ligation and perforation; colloid; crystalloid; inflammation; lipopolysaccharide; liver; microcirculation