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A Method for Generating Pulmonary Neutrophilia Using Aerosolized Lipopolysaccharide
Published on: December 15, 2014
Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation
Silvie Kremserova1, Tomas Perecko2, Karel Soucek3
1Department 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.
Abstract:
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.
Insights
Myeloperoxidase (MPO) regulates lung inflammation during sepsis by affecting neutrophil lifespan and chemokine accumulation. MPO deficiency increases neutrophil infiltration and RANTES levels in the lungs.
Area of Science:
- Immunology
- Pulmonary Medicine
- Inflammation Research
Background:
- Sepsis-induced systemic inflammation frequently leads to acute lung injury and failure, a major cause of mortality.
- Neutrophils are critical effectors in pulmonary failure, but the precise mechanisms of their action remain unclear.
- Myeloperoxidase (MPO), an enzyme abundant in neutrophil granules, is implicated in inflammatory processes.
Purpose of the Study:
- To investigate the role of myeloperoxidase (MPO) in modulating acute pulmonary inflammation.
- To elucidate the mechanisms by which MPO influences neutrophil behavior and lung injury in response to lipopolysaccharide (LPS).
Main Methods:
- Utilized MPO-deficient mice and wild-type littermates subjected to intranasal lipopolysaccharide (LPS) administration.
- Assessed lung inflammation by quantifying neutrophil infiltration and measuring inflammatory markers in bronchoalveolar lavage fluid (BALF).
- Evaluated neutrophil cell death via phosphatidylserine surface expression.
Main Results:
- MPO-deficient mice exhibited significantly higher neutrophil infiltration into the airways compared to wild-type mice.
- Elevated levels of RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) were observed in the BALF of MPO-deficient mice.
- No significant differences in total protein or other selected pro-inflammatory cytokines were found in BALF between the groups.
- MPO-deficient neutrophils demonstrated a reduced rate of cell death, indicated by decreased phosphatidylserine expression.
Conclusions:
- MPO plays a crucial role in regulating pulmonary inflammation, independent of its antimicrobial functions.
- MPO's influence on neutrophil lifespan and the accumulation of chemotactic factors contributes to its regulatory role in lung inflammation.
- Targeting MPO activity may offer therapeutic strategies for managing sepsis-induced acute lung injury.
