Severe respiratory viral infections during childhood have been associated with significantly increased risk of asthma. Infection with the paramyxovirusSendai virus (SeV) leads to development of post-viral asthma in mice. Essential to this pathway is production of anti-viral IgE. Removal of IgE in humans resulted in reduced asthma exacerbations in a clinical trial. The role of IgE in the acute anti-viral immune response is unknown; we, therefore, hypothesized that IgE is essential for induction of pulmonary vascular leak during a respiratory viral infection.
C57BL6 (WT) or IgE–/– mice were inoculated with SeV. One group of IgE–/– mice received 3mcg anti-ova IgE on day 5 post inoculation (PI) SeV followed 1 day later with 10mcg of OVA intranasally. On day 8 PI, Evans Blue Dye (EBD; binds albumin to quantify vascular leak) was given intravenously, and 1 hour later pulmonary vasculature flushed with PBS, and EBD concentration in lung homogenates determined by spectrophotometry. EBD extravasation in lung after viral infection was compared to uninfected WT and IgE–/–mice (Fold EBD).
As measured by fold EBD, WT mice developed vascular leak, which was completely abrogated in IgE–/– mice (3.43±0.18 v. 1.26±0.20, mean±SEM fold EBD concentration, WT v. IgE–/–, p<0.0001, n>4). Administration of IgE and antigen to IgE–/– mice restored vascular leak (3.31±0.08, p=0.54 v. WT; p<0.0001 v. IgE–/–alone, n>4).
IgE is required for development of pulmonary vascular leak during a severe respiratory viral infection. Ongoing projects will identify the cell(s) responsible for the leak.