Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan.

OBJECTIVE AND
DESIGN: This study examines the role of myeloperoxidase (MPO), a major constituent of neutrophils that generates hypochlorous acid, in neutrophil recruitment into the zymosan-exposed lung of mice.
METHODS: Mice were inoculated intranasally with zymosan. The accumulation of neutrophils and other inflammatory cells within the lung was analyzed by flow cytometry. Macrophage inflammatory protein 2 (MIP-2) expression in the lung was quantified, and the contribution of this chemokine to neutrophil accumulation was examined by intranasal administration of MIP-2 antibody. The cellular sources of MIP-2 were identified, and the production of this chemokine from macrophages and neutrophils was quantified in vitro.
RESULTS: Zymosan exposure led to greater neutrophil infiltration into the lungs of MPO(-/-) mice relative to wild-type mice. This was associated with higher MIP-2 levels in the mutant mice. Neutralization of MIP-2 in vivo significantly reduced neutrophil infiltration. Neutrophils from MPO(-/-) mice produced more MIP-2, and the production was reduced when MPO was added exogenously.
CONCLUSIONS: MPO deficiency results in severe lung inflammation in mice exposed to zymosan. Relatively high MIP-2 levels likely contribute to the strong inflammatory response in these animals.