INTERFERON-GAMMA REGULATES PLATELET ENDOTHELIAL-CELL ADHESION MOLECULE-1 EXPRESSION AND NEUTROPHIL INFILTRATION INTO HERPES-SIMPLEX VIRUS-INFECTED MOUSE CORNEAS

In a mouse model of herpes simplex virus (HSV) 1 corneal infection, ti ssue destruction results from a CD4(+) T cell-mediated chronic inflamm ation, in which interleukin 2 and interferon (IFN)gamma are requisite inflammatory mediators and polymorphonuclear leukocytes (PMN) are the predominant infiltrating cells. In vivo neutralization of IFN-gamma re lieved inflammation at least in part through a specific block of PMN e xtravasation into HSV-1-infected corneas. Intercellular adhesion molec ule (ICAM) 1 and platelet endothelial cell adhesion molecule (PECAM) 1 were upregulated on the vascular endothelium of inflamed corneas. Red uced PMN extravasation in anti-IFN-gamma-treated mice was associated w ith a dramatic reduction of PECAM-1 but not ICAM-1 expression on vascu lar endothelium. PMN accumulated in the lumen of corneal vessels after in vivo IFN-gamma neutralization. PECAM-1 was readily detectable on P MN inside the vessels but was not detectable on PMN that extravasated into the infected cornea. Moreover, now cytometric analysis revealed r educed PECAM-1 expression but elevated major histocompatibility comple x class I expression on PMN that recently extravasated into the perito neal cavity when compared with PMN in the peripheral blood. We conclud e that IFN-gamma contributes to HSV-1-induced corneal inflammation by facilitating PMN infiltration; this appears to be accomplished through upregulation of PECAM-1 expression on the vascular endothelium; and P MN downregulate PECAM-1 expression during the process of extravasation .