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Impaired neutrophil exocytosis in patients with severe pneumonia
B Zimmermann1, K Dalhoff, J Braun
1Department of Medicine II, Medical University of Lübeck, Germany.
Objective:
Polymorphonuclear neutrophils (PMN) are one of the major effector cells of pulmonary defence against bacterial infection. To determine whether neutrophil function is impaired in patients with severe pneumonia, we assessed the two main partial functions exocytosis and oxidative response (ROS production) in isolated neutrophils from the peripheral venous blood of pneumonia patients and healthy volunteers. In addition, pulmonary neutrophils and peripheral neutrophils were compared in pneumonia patients.
Patients And Methods:
Twenty-one patients with severe pneumonia were enrolled in the study. Eleven patients were mechanically ventilated, ten patients breathed spontaneously. For comparison, ten healthy adults were studied. The release of two markers of neutrophil exocytosis, lactoferrin and myeloperoxidase (MPO), with and without stimulation by phorbol-myristate-acetate (PMA), was determined using immunoluminometric assays. ROS production was quantified using luminol-enhanced chemiluminescence. In addition, the clinical severity of pneumonia was correlated to neutrophil exocytosis.
Results:
With regard to blood neutrophils, both basal and PMA-stimulated exocytosis were significantly impaired in pneumonia patients compared to healthy volunteers (basal lactoferrin secretion in pneumonia patients: 0.25+/-0.36 pg/PMN versus controls: 1.17+/-0.78 pg/PMN, p<0.01). In contrast, both basal and PMA-stimulated ROS production were increased in patients compared to controls (spontaneous chemiluminescence in pneumonia patients: 13.6x10(5) cpm versus controls: 5.5x10(5) cpm). In pneumonia patients, the pulmonary neutrophils released significantly more lactoferrin, MPO and ROS compared to blood neutrophils (basal lactoferrin secretion of pulmonary neutrophils: 1.19+/-1.55 pg/PMN; p<0,01). However, after stimulation with PMA the exocytosis of pulmonary and blood neutrophils was similar. The severity of pneumonia and prognostic indices like albumin were inversely correlated to the release of lactoferrin in blood neutrophils (p<0,05).
Conclusion:
In patients with severe pneumonia, the exocytosis of blood neutrophils was significantly impaired. In contrast to this, the oxidative response was increased. Impaired bone marrow maturation of neutrophils during severe infection, perhaps due to shortened maturation time, could explain these findings.
Insights
In severe pneumonia patients, blood neutrophils show impaired exocytosis but increased oxidative response. Pulmonary neutrophils are more active than blood neutrophils, suggesting altered neutrophil function during severe infection.
Area of Science:
- Immunology
- Pulmonary Medicine
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMN) are critical for lung defense against bacterial infections.
- Neutrophil dysfunction can compromise the immune response in severe pneumonia.
- Understanding neutrophil function is key to improving pneumonia treatment.
Purpose of the Study:
- To investigate neutrophil exocytosis and oxidative response (ROS production) in severe pneumonia patients.
- To compare the function of pulmonary and peripheral neutrophils in pneumonia patients.
- To correlate neutrophil function with pneumonia severity.
Main Methods:
- Isolated neutrophils from 21 severe pneumonia patients and 10 healthy controls.
- Assessed exocytosis (lactoferrin, MPO release) and ROS production (chemiluminescence).
- Compared blood neutrophils with pulmonary neutrophils in pneumonia patients.
Main Results:
- Blood neutrophils in pneumonia patients had impaired basal and stimulated exocytosis compared to controls.
- ROS production was significantly increased in pneumonia patients' blood neutrophils.
- Pulmonary neutrophils exhibited higher lactoferrin, MPO, and ROS release than blood neutrophils.
Conclusions:
- Severe pneumonia impairs blood neutrophil exocytosis while enhancing oxidative response.
- Pulmonary neutrophils are more responsive than peripheral neutrophils in pneumonia.
- Altered neutrophil maturation during severe infection may explain these functional changes.