Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site.

Department of Free Radical Pathophysiology Institute of Biophysics Academy of Sciences of the Czech Republic 61265 Brno Czech Republic; Department of Experimental Biology Faculty of Science Masaryk University 61137 Brno Czech Republic; International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno 65691 Brno Czech Republic

Department of Free Radical Pathophysiology Institute of Biophysics Academy of Sciences of the Czech Republic 61265 Brno Czech Republic; International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno 65691 Brno Czech Republic

Department of Internal Medicine School of Medicine University of California Davis CA 95616 USA

Heart Center University of Cologne 50937 Cologne Germany

International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno 65691 Brno Czech Republic; Department of Cytokinetics Institute of Biophysics Academy of Sciences of the Czech Republic 61265 Brno Czech Republic

International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno 65691 Brno Czech Republic; Heart Center University of Cologne 50937 Cologne Germany

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Myeloperoxidase Deficiency Alters the Process of the Regulated Cell Death of Polymorphonuclear Neutrophils