Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

• Published in: Virology journal Vol. 10; no. 1; p. 322
• Main Authors: Loke, Wai Mun, Chow, Angelia Yee, Lam Mok Sing, Karen, Lee, Chung-Yung J, Halliwell, Barry, Lim, Erle CH, Quek, Amy ML, Ooi, Eng Eong, Seet, Raymond CS
• Format: Journal Article
• Language: English
• Published: England Springer-Verlag 30.10.2013; BioMed Central Ltd; BioMed Central
• Subjects: Adult; adults; antigens; Arachidonate 5-Lipoxygenase - biosynthesis; Arachidonic acid; blood serum; C-reactive protein; C-Reactive Protein - analysis; Care and treatment; Case-Control Studies; Cells, Cultured; chemotaxis; Colleges & universities; Comparative analysis; Dengue; Dengue - classification; Dengue - physiopathology; Dengue fever; Female; Health aspects; Heart attacks; Heat; Humans; in vitro studies; Infections; Leukotriene B4 - blood; Male; Medical research; Medicine, Experimental; Membranes; metabolites; neutrophils; Neutrophils - metabolism; Neutrophils - virology; patients; Plasma; Proteins; Serotyping; Standard deviation; therapeutics; Unsaturated fatty acids; Viruses; United Kingdom
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-10-322

BACKGROUND: Leukotriene B₄, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B₄and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age--matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils. RESULTS: Plasma leukotriene B₄was elevated during the febrile stages of dengue infection compared to levels during convalescence and in study controls. Plasma leukotriene B₄also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B₄; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Pre-incubation of either live or heat-inactivated DENV-2 resulted in reduced leukotriene B₄release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B₄was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5-lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B₄production. CONCLUSION: These findings provide important clinical and mechanistic data on the involvement of 5-lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings.