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 ne utrophils. Because neutrophil-mediated liver injury during endotoxemia is dependent on transmigration, we investigated the role of PECAM-1 i n the pathophysiology of endotoxin-induced liver injury. Male C3Heb/Fe J mice were treated with galactosamine (Gal) and endotoxin (ET) (700 m g/kg Gal/100 mu g/kg ET), and liver sections were stained for PECAM-1 expression. Control livers showed the presence of PECAM-1 on endotheli al cells of large vessels but not in sinusoids. Gal/ET treatment did n ot change the expression pattern of PECAM-1. Gal/ET-induced liver inju ry (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 ef fect on sequestration and transmigration of neutrophils in sinusoids o r the margination of neutrophils in large vessels. In contrast, 2H8 in hibited glycogen-induced neutrophil migration into the peritoneum by 7 4%; this effect correlated with PECAM-1 expression in the intestinal v asculature. Thus PECAM-1 is neither expressed nor inducible in hepatic sinusoids and is consequently not involved in neutrophil transmigrati on in the liver during endotoxemia. On the other hand, expression of P ECAM-1 in mesenteric veins is critical for peritoneal neutrophil accum ulation.