Role of PECAM-1 (CD31) in neutrophil transmigration in murine models of liver and peritoneal inflammation.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is thought to be critical for transendothelial migration of leukocytes, including neutrophils. Because neutrophil-mediated liver injury during endotoxemia is dependent on transmigration, we investigated the role of PECAM-1 in the pathophysiology of endotoxin-induced liver injury. Male C3Heb/FeJ mice were treated with galactosamine (Gal) and endotoxin (ET) (700 mg/kg Gal/100 micrograms/kg ET), and liver sections were stained for PECAM-1 expression. Control livers showed the presence of PECAM-1 on endothelial cells of large vessels but not in sinusoids. Gal/ET treatment did not change the expression pattern of PECAM-1. Gal/ET-induced liver injury (area of necrosis: 38 +/- 3%) was not attenuated by treatment with 3 mg/kg of the antimurine PECAM-1 antibody 2H8. The antibody had no effect on sequestration and transmigration of neutrophils in sinusoids or the margination of neutrophils in large vessels. In contrast, 2H8 inhibited glycogen-induced neutrophil migration into the peritoneum by 74%; this effect correlated with PECAM-1 expression in the intestinal vasculature. Thus PECAM-1 is neither expressed nor inducible in hepatic sinusoids and is consequently not involved in neutrophil transmigration in the liver during endotoxemia. On the other hand, expression of PECAM-1 in mesenteric veins is critical for peritoneal neutrophil accumulation.
Chosay
J G
JG
Department of Pharmacology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49007, USA.
Fisher
M A
MA
Farhood
A
A
Ready
K A
KA
Dunn
C J
CJ
Jaeschke
H
H
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D006520:Hepatitis, Animal / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000473:pathology / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*
D019408:Platelet Endothelial Cell Adhesion Molecule-1