The role of endothelial cell-derived inflammatory and vasoactive mediators in the pathogenesis of bluetongue

Christopher D. DeMaula, Christian M. Leutenegger, Kyle R. Bonneau, Nigel J Maclachlan

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Bluetongue is an insect-transmitted disease of sheep and wild ruminants that is caused by bluetongue virus (BTV). Cattle are asymptomatic reservoir hosts of BTV. Infection of lung microvascular endothelial cells (ECs) is central to the pathogenesis of BTV infection of both sheep and cattle, but it is uncertain as to why sheep are highly susceptible to BTV-induced microvascular injury, whereas cattle are not. Thus, to better characterize the pathogenesis of bluetongue, the transcription of genes encoding a variety of vasoactive and inflammatory mediators was quantitated in primary ovine lung microvascular ECs (OLmVECs) exposed to BTV and/or inflammatory mediators. BTV infection of OLmVECs increased the transcription of genes encoding interleukin- (IL) 1 and IL-8, but less so IL-6, cyclooxygenase-2, and inducible nitric oxide synthase. In contrast, we previously have shown that transcription of genes encoding all of these same mediators is markedly increased in BTV-infected bovine lung microvascular ECs and that BTV-infected bovine ECs produce substantially greater quantities of prostacyclin than do sheep ECs. Thus, sheep and cattle were experimentally infected with BTV to further investigate the role of EC-derived vasoactive mediators in the pathogenesis of bluetongue. The ratio of thromboxane to prostacyclin increased during BTV infection of both sheep and cattle, but was significantly greater in sheep (P = 0.001). Increases in the ratio of thromboxane to prostacyclin, indicative of enhanced coagulation, coincided with the occurrence of clinical manifestations of bluetongue in BTV-infected sheep. The data suggest that inherent species-specific differences in the production and activities of EC-derived mediators contribute to the sensitivity of sheep to BTV-induced microvascular injury.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalVirology
Volume296
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Bluetongue virus
  • Cattle
  • Cytokines
  • Endothelium
  • Sheep

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'The role of endothelial cell-derived inflammatory and vasoactive mediators in the pathogenesis of bluetongue'. Together they form a unique fingerprint.

  • Cite this