PEG-fDAO Reduces Lung Inflammation in Chronic Granulomatous Disease Mice Post Challenge with Nonviable Candida Albicans

Abstract We previously reported that polyethylene glycol-conjugated recombinant porcine D-amino acid oxidase (PEG-pDAO) could supply reactive oxygen species (ROS) to defective NADPH oxidase in neutrophils of patients with chronic granulomatous disease (CGD), and neutrophils regain bactericidal activity in vitro. In the present study, we employed an in vivo nonviable Candida albicans (nCA)-induced lung inflammation model using gp91-phox knockout CGD mice and novel PEG conjugates of Fusarium spp. D-amino acid oxidase (PEG-fDAO), rather than PEG-pDAO. Using three experimentation strategies with the in vivo lung inflammation model, the mouse body weight, lung weight, and lung pathology were evaluated to confirm the efficacy of ROS-generating enzyme replacement therapy with PEG-fDAO. The lung weight and pathological findings were significantly ameliorated by the administration of PEG-fDAO followed by intraperitoneal injection of D-phenylalanine or D-proline. These data suggest that PEG- fDAO with the function of targeted delivery to the nCA-induced inflammation site is applicable in the treatment of inflammation in CGD in vivo.