Neutrophil adhesion is impaired in the mesentery but not in the liver sinusoids of portal hypertensive rats.
Altered leukocyte/cytokine response to inflammation has been observed in human and experimental portal hypertension. The aim of this study was to characterize leukocyte adhesion in portal hypertensive (PPVL) rats stimulated with endotoxin. Leukocyte rolling, adhesion, and migration assessed by intravital microscopy were impaired in mesenteric venules after lipopolysaccharide administration (150 microg/kg) in PPVL vs. sham-operated rats. Analysis of leukocyte L-selectin expression and soluble L-selectin showed that this defective adhesion was related to increased L-selectin shedding. In vitro experiments using isolated leukocytes treated with phorbol 12-myristate 13-acetate showed that monocytes and neutrophils but not lymphocytes were hyperreactive to cell activation, as measured by CD11b overexpression and increased L-selectin shedding in PPVL rats. However, neutrophil emigration in liver sinusoids and in the lung 3 h after endotoxin injection were similar in both groups of animals. Thus the alterations in leukocyte activation and adhesion molecule expression observed in this study may contribute to a better understanding of the higher susceptibility and severity of bacterial infections in cirrhotic patients with portal hypertension.
Pérez-Del-Pulgar
S
S
Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives, Hospital Clinic, 08036 Barcelona, Spain.
Pizcueta
P
P
Engel
P
P
Bosch
J
J
Rodés
J
J
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D006975:Hypertension, Portal / Q000473:pathology / Q000503:physiopathology*; D019041:L-Selectin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008102:Liver Circulation; D008168:Lung / Q000201:enzymology; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014699:Venules / Q000503:physiopathology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D009195:Peroxidase