title: 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.
abstract: The effect of herpes virus infection on human dermal microvascular endothelial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of herpes-associated erythema multiforme. After infection of human dermal microvascular endothelial cells with native herpes virus and overnight culture, 60%--90% of human dermal microvascular endothelial cells showed cytopathic effects. 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-infected peripheral blood mononuclear cells left characteristic plaques on the human dermal microvascular endothelial cell monolayer; however, very few human dermal microvascular endothelial cells (1%--3%) were infected. Adhesion molecule expression of human dermal microvascular endothelial cells cocultivated with herpes-virus-infected peripheral blood mononuclear cells demonstrated a 5-fold increase in CD54 expression, a 2-fold increase in HLA class I expression, but no change of CD31 by fluorescence-activated cell sorter analysis. Incubation of human dermal microvascular endothelial cells with ultraviolet-C irradiated herpes-virus-infected peripheral blood mononuclear cells had no effect on morphology or adhesion molecule expression levels. Changes of adhesion molecule expression by direct infection or cocultivation with peripheral blood mononuclear cells (with native and ultraviolet-C inactivated herpes virus infection) were also documented at the mRNA level. Adhesion assays demonstrated an increased binding of herpes-virus-infected peripheral blood mononuclear cells versus noninfected peripheral blood mononuclear cells to noninfected human dermal microvascular endothelial cells. Our results suggest that incubation of herpes-virus-infected peripheral blood mononuclear cells with human dermal microvascular endothelial cells induces significant upregulation of CD54 and major histocompatibility complex class I molecules in the surrounding noninfected human dermal microvascular endothelial cells, which is associated with an increased binding of peripheral blood mononuclear cells. Our in vitro findings may serve as a model for herpes-associated erythema multiforme possibly explaining the dermal inflammatory reaction seen in that condition.
authors.affiliation: Institute of Hygiene, University of Innsbruck, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Larcher
authors.forename: A
authors.initials: A
authors.lastname: Gasser
authors.forename: R
authors.initials: R
authors.lastname: Hattmannstorfer
authors.forename: P
authors.initials: P
authors.lastname: Obexer
authors.forename: C
authors.initials: C
authors.lastname: Fürhapter
authors.forename: P
authors.initials: P
authors.lastname: Fritsch
authors.forename: N
authors.initials: N
authors.lastname: Sepp
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D004892:Erythema Multiforme / Q000821:virology; D006561:Herpes Simplex / Q000097:blood*; D018259:Herpesvirus 1, Human; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000821:virology*; D008833:Microcirculation / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012867:Skin / Q000166:cytology*
chemical_list: D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1