Insights into potential causes of vascular hyperpermeability in dengue

Together with bound plasma proteins such as albumin, fibrinogen, and orosomucoid, the EGL forms a physiological barrier between the intravascular compartment and the interstitium, and damage and degradation may increase vascular permeability [5,6]. Furthermore, increased blood levels of HA, syndecan-1 and CS in dengue patients were proportional to disease severity, further suggesting that EGL is damaged in clinical disease [5,6,10]. In dengue patients, a significant increase in the peripheral circulation of canonical proteins that are associated with neutrophil degranulation, and granular proteins such as neutrophil elastase and α-defensin 1 were observed in DSS cases compared to either healthy controls or uncomplicated dengue cases [26–28]. In a mouse model, simultaneous inhibition of C-type lectin domain family 5 member A (CLEC5A, a pattern recognition receptor) and TLR 2, receptors involved in mediating neutrophil activation and NETs formation, significantly reduced vascular permeability and improved survival [30].