Phenotyping of mice with genetic defects relevant to allergic diseases: Proteinase 3/neutrophil elastase double-knockout mice.

Understanding the type of cellular inflammation in acute severe asthma has important implications not only for the treatment of disease but also for its prevention. Although there is clear evidence demonstrating distinct infiltration and presence of neutrophils in asthma, their specific function for the disease is not fully elucidated. The granule-associated elastase homologues neutrophil elastase and proteinase 3 are involved in immune defense reactions of neutrophils. The use of genetically engineered animal models to explore the function of genes and for the selection of appropriate drug targets holds great promise in accelerating the development of valuable therapies. Model organisms, especially the mouse, have proven to be important tools to learn more about gene functions. Understanding the role of neutrophils and its proteases has important implication not only for the treatment of asthma but also for its prevention. In this study the role of neutrophil proteases in an animal model of asthma was investigated. We mainly focused on type I allergic reactions. Intrestingly, we found that after aerosol challenge of mice lacking the neutrophil proteases, Elastase and proteinase 3, normal attending of neutrophils in bronchial lumen can be followed by recruitment /infiltration of the normal levels of eosinophils. Thus, surprisingly, our primary hypothesis that impaired neutrophils may cause significant changes in eosinophils infiltration in bronchoalveolar lavage was not confirmed. This observation raises the hypothesis that neutrophil serine proteases may exert more subtle effects such a delayed cellular clearance in the inflammation site