Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation

Paradigms of eosinophil effector function in the lungs of asthma patients i nvariably depend on activities mediated by cationic proteins released from secondary granules during a process collectively referred to as degranulati on. In this study, we generated knockout mice deficient for eosinophil pero xidase (EPO) to assess the role(s) of this abundant secondary granule prote in in an OVA-challenge model. The loss of EPO had no effect on the developm ent of OVA-induced pathologies in the mouse. The absence of phenotypic cons equences in these knockout animals extended beyond pulmonary histopathologi es and airway changes, as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness after provocation with methacholine. In addition , EPO-mediated oxidative damage of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar lavage from OVA-treated wild-type mi ce was <10% of the levels observed in bronchoalveolar lavage recovered from asthma patients. These data demonstrate that EPO activities are inconseque ntial to the development of allergic pulmonary pathologies in the mouse and suggest that degranulation of eosinophils recruited to the lung in this mo del does not occur at levels comparable to those observed in humans with as thma.