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

Abstract

SummaryIn 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)~/are requisite inflanunatory mediators and polymorphonuclear leukocytes (PMN) are the predominant infiltrating cells. In vivo neutralization of IFN-y reheved inflammation at least in part through a specific block of PMN extravasation into HSV-l-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 P M N extravasation in anti-IFN-',/-treated mice was associated with a dramatic reduction of PECAM-1 but not ICAM-1 expression on vascular endothelium. P M N accumulated in the lumen of corneal vessels after in vivo IFN-~/neutralization. PECAM-1 was readily detectable on P M N inside the vessels but was not detectable on P M N that extravasated into the infected cornea. Moreover, flow cytometric analysis revealed reduced PECAM-1 expression but elevated major histocompatibility complex class I expression on P M N that recently extravasated into the peritoneal cavity when compared with P M N in the peripheral blood. We conclude that IFN-y contributes to HSV-l-induced corneal inflammation by facilitating P M N 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.

Distinct Roles for PECAM-1, ICAM-1, and VCAM-1 in Recruitment of Neutrophils and Eosinophils to the Cornea in Ocular Onchocerciasis (River Blindness)

“…Our findings that PECAM-1 mediates neutrophil extravasation from limbal vessels are consistent with those of Tang and Hendricks (13), who demonstrated that PECAM-1 expression mediates neutrophil recruitment to the cornea in herpes simplex keratitis and that both are regulated by IFN-␥. PECAM-1 is also important in neutrophil infiltration to other tissues, including the lungs and peritoneal cavity (20 -23).…”

On the influence of neutrophils in corneas with necrotizing HSV-1 keratitis following amniotic membrane transplantation

“…Tlymphocytes are mediating this form of corneal inflammation, and CD4 + T-cell derived cytokines such as interferon (IFN)-γ and interleukin (IL)-2 are critical for the development of the disease (Hendricks et al, 1992;Niemialtowski and Rouse, 1992;Tang et al, 1997;Tang and Hendricks, 1996). Polymor-phonuclear neutrophils (PMN) are the most prominent infiltrating cell type seen in HSK (Meyers-Elliott and Chitjian, 1981) and are associated with elimination of HSV-1 from the infected eye Tumpey et al, 1996).…”

CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection

“…Although PMNs are one of the initial cells that traffic to the cornea [3], CD4 + and CD8 + T lymphocytes are thought to be key components in the development of lesions associated with herpetic stromal keratitis [4][5][6][7]. Th2 cytokines exacerbate HSV-1 infection whereas Th1 cytokines are principally produced by those cells infiltrating the infected tissue and contribute towards resistance to virus replication and spread [8][9][10].…”