Myeloperoxidase (MPO) delays neutrophil apoptosis and prolongs acute pulmonary inflammation

Abstract

We have identified MPO as a suppressor of apoptosis in human neutrophils in vitro. We investigated the impact of MPO on neutrophil apoptosis in vivo and on the resolution of neutrophil‐mediated inflammation in mice. Intravenous injection of MPO (5 nmol/kg) into conscious rats did not affect mean arterial blood pressure and the number of circulating leukocytes, whereas it significantly reduced the number of apoptotic neutrophils assessed ex vivo at 60 min post‐MPO. In a mouse model of spontaneously resolving (within 5 days) acute lung injury, intratracheal instillation of carrageenan evoked massive infiltration of neutrophils into the airspace and tissues, and alveolar edema. Intratracheal injection of MPO alone produced only minimal inflammatory cell accumulation in the airways, whereas it prolonged carrageenan‐induced inflammation. Thus, the number of neutrophils in the bronchoalveolar lavage (BAL) fluid and BAL fluid protein levels were still markedly elevated at Day 5 post‐carragenan plus MPO as compared with mice that were injected carrageenan only. The percentage of annexin‐V‐positive neutrophils in BAL fluid was significantly lower in carragenan plus MPO‐treated mice than in carrageenan‐treated mice. Our results indicate that MPO supression of neutrophil apoptosis can profoundly affect the duration of the inflammatory response and add a novel facet to the MPO biology. (Support: CIHR MOP‐64283).