Interaction of HSV-1 infected peripheral blood mononuclear cells with cultured dermal microvascular endothelial cells: a potential model for the pathogenesis of HSV-1 induced erythema multiforme

The effect of herpes virus infection on human dermal microvascular endothel ial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of her pes-associated erythema multiforme, After infection of human dermal microva scular endothelial cells with native herpes virus and overnight culture, 60 %-90% of human dermal microvascular endothelial cells showed cytopathic eff ects. HLA class I molecules and CD31 (PECAM-1) surface expression in herpes virus-infected endothelial cells were substantially downregulated, whereas CD54 (ICAM-1) remained unchanged, Cocultivation with herpes-virus-1-infecte d peripheral blood mononuclear cells left characteristic plaques on the hum an dermal microvascular endothelial cell monolayer; however, very few human dermal microvascular endothelial cells (1%-3%) were infected. Adhesion mol ecule expression of human dermal microvascular endothelial cells cocultivat ed with herpes-virus-infected peripheral blood mononuclear cells demonstrat ed a 5-fold increase in CD54 expression, a 2-fold increase in HLA class I e xpression, but no change of CD31 by fluorescence-activated cell sorter anal ysis, Incubation of human dermal microvascular endothelial cells with ultra violet-C irradiated herpes-virus-infected peripheral blood mononuclear cell s had no effect on morphology or adhesion molecule expression levels. Chang es of adhesion molecule expression by direct infection or cocultivation wit h peripheral blood mononuclear cells (with native and ultraviolet-C inactiv ated herpes virus infection) were also documented at the mRNA level. Adhesi on assays demonstrated an increased binding of herpes-virus-infected periph eral blood mononuclear cells versus noninfected peripheral blood mononuclea r cells to noninfected human dermal microvascular endothelial cells. Our re sults suggest that incubation of herpes-virus-infected peripheral blood mon onuclear cells with human dermal microvascular endothelial cells induces si gnificant upregulation of CD54 and major histocompatibility complex class I molecules in the surrounding noninfected human dermal microvascular endoth elial cells, which is associated with an increased binding of peripheral bl ood mononuclear cells. Our in vitro findings may serve as a model for herpe s-associated erythema multiforme possibly explaining the dermal inflammator y reaction seen in that condition.