Activation of vascular endothelial cells by IL-1alpha released by epithelial cells infected with respiratory syncytial virus.
Although pulmonary inflammation is a serious, sometimes life-threatening, consequence of respiratory syncytial virus (RSV) infection, the mechanisms involved are not well understood. Since the process of inflammation is initiated by a complex series of events including the activation of specific adhesion molecules on vascular endothelium, we searched for endothelial cell-activating factors released from RSV-infected epithelial cells. We demonstrate here that vascular endothelial cells exposed to culture supernatants from RSV-infected pulmonary epithelial A549 cells are activated to express increased cell surface ICAM-1, and to a lesser extent, VCAM-1 and E-selectin. IL-1alpha was identified as the predominant endothelial cell-activating factor by pretreating epithelial cell supernatants with anti-IL-1alpha antibody. The preferential upregulation of endothelial ICAM-1 (relative to VCAM-1 and E-selectin) by RSV-infected epithelial cell supernatants was replicated by recombinant IL-1alpha thus confirming IL-1alpha as a major endothelial cell-activating cytokine released by RSV-infected epithelial cells. Il-1alpha mediated endothelial cell activation is thus a likely contributory event in the initiation of leukocyte inflammation associated with RSV infection.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
Cheng-Hsien
CH
Chang
Yan
Y
Huang
Robert
R
Anderson
D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017077:Culture Media, Conditioned; D019040:E-Selectin; D007375:Interleukin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1