Prostaglandin E1 protects against ischemia-reperfusion injury of the liver by inhibition of neutrophil adherence to endothelial cells.
BACKGROUND
This study investigates the protective mechanism of prostaglandin E1 (PGE1) against hepatic ischemia-reperfusion injury in vivo. It has been demonstrated that activated leukocytes contribute to ischemia-reperfusion injury, and that administration of the monoclonal antibody (mAb) for adhesion molecules reduces the injury by inhibiting leukocyte-endothelial cell adhesion. We therefore attempted to find out whether PGE1 has an effect on the inhibition of neutrophil adherence to endothelial cells after reperfusion.


METHODS
We administered anti-intercellular adhesion molecule 1 (ICAM-1) mAb, antiserum against rat polymorphonuclear leukocytes, or PGE1 to a rat model of left lobar ischemia for 60 min followed by reperfusion. Leukocyte adherence was observed by intravital fluorescence microscopy. The effect of PGE1 on the expression of adhesion molecules was analyzed by immunohistochemistry and flow cytometry.


RESULTS
Ischemia-reperfusion caused endothelial dysfunction and hepatocellular injury with leukostasis in postsinusoidal venules. Anti-ICAM-1 mAb administration or leukopenia ameliorated both the hepatocellular injury and endothelial dysfunction. Although PGE1 administration did not affect the serum interleukin-8 level, it significantly decreased hepatic injury and leukostasis in the reperfused liver. Immunohistochemical findings showed that PGE1 decreased ICAM-1 expression on endothelial cells, but did not affect lymphocyte function-associated antigen 1, and membrane attack complex 1 on neutrophils in flow cytometric analysis.


CONCLUSIONS
We conclude that PGE1 protects the liver against ischemia-reperfusion injury by reducing leukocyte-endothelial cell adhesion via down-modulation of ICAM-1 expression on the endothelium.
Natori
S
S
Second Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan.
Fujii
Y
Y
Kurosawa
H
H
Nakano
A
A
Shimada
H
H
D000527:Alprostadil / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood; D007511:Ischemia / Q000473:pathology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D001219:Aspartate Aminotransferases; D000527:Alprostadil