In vivo role of myeloperoxidase for the host defense.

Myeloperoxidase (MPO) is located within neutrophils capable of producing HOCl. To define the in vivo role of MPO, we have generated MPO-knockout (MPO-KO) mice. The mice without MPO developed normally. However, MPO-KO mice showed severely reduced cytotoxicity to various microorganisms such as Candida albicans, Aspergillus fumigatus, and Klebsiella pneumoniae, demonstrating that MPO-dependent oxidative system is important for host defense against fungi and bacteria, although the effect varies from species to species of pathogens. To compare the importance of MPO and NADPH-oxidase for host defense, MPO-KO and chronic granulomatous disease (CGD) mice were infected with different doses of C. albicans, and their infection severity was analyzed. CGD mice exhibited increased mortality and tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms. Interestingly, at the highest dose, the mortality of MPO-KO mice was comparable to CGD mice, but was the same as normal mice at the lowest dose. These results suggest that MPO and NADPH-oxidase are equally important for early host defense against a large inocula of Candida.