Different anti-apoptotic effects of house dust mite allergen on eosinophil apoptosis between atopic and non-atopic asthmatic subjects

House dust mite is a major allergen in allergic diseases such as asthma. In this study, we investigated the effects of house dust mite on constitutive eosinophil apoptosis in normal and asthmatic subjects. We classified asthmatic subjects into those with atopic and non-atopic asthma depending on the presence of DP-specific IgE or/and DF-specific IgE in serum. Both blood and bronchoalveolar lavage fluid (BALF) eosinophils in atopic asthma were elevated when compared with normal and non-atopic eosinophils. Dermatophagoides pteronissinus extract (DP) inhibited constitutive eosinophil apoptosis of atopic asthmatic subjects, but not that of normal and non-atopic subjects. DF had no effect on eosinophil apoptosis in normal and asthmatic subjects. The anti-apoptotic effects of DP were not altered by E64, a cysteine protease inhibitor, or aprotinin, a serine protease inhibitor, and Der p1 and Der p 2 had no effect on eosinphil apoptosis of normal and asthmatic patients, including atopic and not-atopic patients. Anti-apoptotic signaling mediated by DP in atopic asthma was associated with the TLR4/PI3K/Akt/ERK/NF-κB pathway. Activation of procaspase 3 and procaspase 9 was delayed by DP stimulation. Our results indicate that DP induces eosinophilic inflammation by inhibiting eosinophil apoptosis, and that the inhibitory effect is associated with exposure of asthma subjects to DP. A better understanding of the difference between atopic and non-atopic asthma will help elucidate the pathogenesis and develop methods for treatment of asthma.