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, tissue destruction results from a CD4+ T cell-mediated chronic inflammation, 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 relieved inflammation at least in part through a specific block of PMN extravasation into HSV-1-infected corneas. Intercellular adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion molecule (PECAM) 1 were upregulated on the vascular endothelium of inflamed corneas. Reduced PMN extravasation in anti-IFN-gamma-treated mice was associated with a dramatic reduction of PECAM-1 but not ICAM-1 expression on vascular endothelium. PMN accumulated in the lumen of corneal vessels after in vivo IFN-gamma neutralization. PECAM-1 was readily detectable on PMN inside the vessels but was not detectable on PMN that extravasated into the infected cornea. Moreover, flow cytometric analysis revealed reduced PECAM-1 expression but elevated major histocompatibility complex class I expression on PMN that recently extravasated into the peritoneal cavity when compared with PMN in the peripheral blood. We conclude 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 PMN downregulate PECAM-1 expression during the process of extravasation.
Tang
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Department of Microbiology and Immunology, University of Illinois at Chicago 60612, USA.
Hendricks
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RL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003315:Cornea / Q000098:blood supply; D003318:Corneal Opacity / Q000276:immunology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology*; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008833:Microcirculation / Q000473:pathology; D009504:Neutrophils / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma