Protease-mediated house dust mite allergen-induced reactive oxygen species production by neutrophils

A growing body of evidence indicates that neutrophils may play an important role in the pathogenesis of asthma. However, the involvement of the house dust mite (HDM) in neutrophil activation associated with the pathogenesis of asthma is not fully understood yet. To address this situation, we harvested neutrophils isolated from 15 HDM-sensitized asthmatic subjects and 18 HDM-sensitized nonasthmatic subjects and measured the amounts of neutrophil reactive oxygen species (ROS) production in response to the major HDM allergens Der-f and Der-f1. Der-f and Der-f1 significantly increased ROS production in neutrophils isolated from asthmatic subjects versus nonasthmatic subjects. To assess the involvement of Der-f-specific IgE antibodies binding to their receptors in HDM allergen-induced ROS production, we examined whether neutrophils produce ROS by cross-linking of cell-bound IgE antibodies with anti-IgE. Treatment with anti-IgE antibodies did not induce ROS production by neutrophils isolated from 6 asthmatic subjects. On the other hand, pretreatment of Der-f with E-64, a cysteine protease inhibitor, eliminated Der-f-induced ROS production. These results suggest that HDM-allergen exposure may result in greater production of ROS in asthmatic patients and may be involved in the pathogenesis of asthma.