Increased serum IgE levels in allergic asthma contribute to inflammation. Neutralizing humanized anti-IgE antibodies, such as Omalizumab, effectively reduce inflammation. In this study we determined the effect of human activated IgE in the presence and absence of Omalizumab on extracellular matrix deposition by human airway smooth muscle cells (8 asthma patients; 8 healthy controls). Confluent cells were stimulated by 5% human pooled serum or IgE (0.1 – 10 ng/ml) in the presence or absence of Omalizumab (1 – 100 ng/ml) for 72 hours in the presence of 3H-proline (0.5 microCi) and extracellular matrix deposition was monitored. Compared to non-stimulated cells, stimulation with 5% serum increased matrix deposition by +42% and IgE dose-dependently increased matrix deposition by max. +38%. Interestingly we observed the stimulatory effect of IgE in airway smooth muscle cells of both healthy controls and asthma patients with no significant difference. When the cells were pre-incubated with Omalizumab for 30 minutes the IgE-induced matrix deposition was dose-dependently reduced. The reductive effect was 100% when ratio of Omalizumab:IgE was 10:1. Furthermore, the inhibitory effect of Omalizumab was similar when applied together with IgE, or even when added 15 minutes after IgE. When added at later time points after IgE addition the inhibitory effect of Omalizumab was reduced but significant until 45 minutes. We observed no difference of either IgE induced matrix deposition or the inhibitory effect of Omalizumab comparing healthy control to asthma patient's cells. Our results indicate that IgE increases airway remodeling and that Omalizumab significantly reduces this effect.
Roth et al. (Thu,) studied this question.