Interferon gamma regulates platelet endothelial cell adhesion molecule 1 expression and neutrophil infiltration into herpes simplex virus-infected mouse corneas

J Exp Med. 1996 Oct 1;184(4):1435-47. doi: 10.1084/jem.184.4.1435.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cornea / blood supply
  • Corneal Opacity / immunology
  • Disease Models, Animal
  • Endothelium, Vascular
  • Female
  • Herpesvirus 1, Human / immunology
  • Histocompatibility Antigens Class I / biosynthesis
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interferon-gamma / pharmacology*
  • Keratitis, Herpetic / immunology*
  • Keratitis, Herpetic / pathology
  • Mice
  • Microcirculation / pathology
  • Neutrophils / immunology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis*
  • Up-Regulation

Substances

  • Histocompatibility Antigens Class I
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma