Bluetongue virus-induced activation of primary bovine lung microvascular endothelial cells.
Bluetongue is an insect-transmitted viral disease of sheep and some species of wild ruminants. Infection of lung microvascular endothelial cells (ECs) is central to the pathogenesis of bluetongue virus (BTV) infection of ruminants, but it is uncertain as to why cattle are resistant to BTV-induced microvascular injury and bluetongue disease. Thus, in order to better understand the pathogenesis of BTV infection of cattle, mRNAs encoding a variety of inflammatory mediators were quantitated by real-time polymerase chain reaction in primary bovine lung microvascular ECs (BLmVECs) exposed to BTV and/or EC-derived mediators. BTV infection of BLmVECs significantly increased the transcription of genes encoding interleukin-1 (IL-1), IL-6, IL-8, cyclooxygenase-2, and inducible nitric oxide synthase. Treatment of BLmVECs with EC-lysates that contained BTV as well as cytokines increased both the incidence of apoptosis and expression of cellular adhesion molecules, as compared to infection of BLmVECs with BTV alone. Thus, BTV infection caused activation of BLmVECs with production of inflammatory mediators that alter the mechanism of cell death of BLmVECs and exert potentially potent effects on blood coagulation. The activities of BTV-induced-EC-derived inflammatory mediators likely contribute to the resistance of cattle to BTV-induced microvascular injury and bluetongue disease.
DeMaula
Christopher D
CD
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Leutenegger
Christian M
CM
Jutila
Mark A
MA
MacLachlan
N James
NJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001819:Bluetongue / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D001820:Bluetongue virus / Q000235:genetics / Q000276:immunology*; D002353:Carrier State / Q000276:immunology / Q000662:veterinary / Q000821:virology; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry / Q000662:veterinary; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
D016207:Cytokines; D019040:E-Selectin; D000949:Histocompatibility Antigens Class II; D007527:Isoenzymes; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases