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Direct and phagocyte-mediated lipid peroxidation of lung surfactant by group B streptococci
R K Bouhafs1, P Rauprich, E Herting
1Department of Immunology, Microbiology, Pathology and Infectious Diseases, Division of Oral and Clinical Bacteriology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.
Abstract:
In newborn infants, group B streptococci (GBS) often cause pneumonia, with polymorphonuclear leukocytes (PMN) migrating into the lungs. Because surfactant therapy may be needed in such patients, we evaluated the interaction between GBS or GBS-stimulated PMN and a surfactant preparation (Curosurf) in vitro. The superoxide production of GBS strains or GBS-activated PMN was measured, using the nitroblue tetrazolium (NBT) test and the subsequent lipid peroxidation (LPO) as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). The growth of GBS in surfactant was determined and related to the LPO. Finally, the effect of LPO on surfactant activity, caused by GBS-stimulated PMN, was assessed by measuring dynamic surface tension in a pulsating bubble surfactometer. Curosurf diminished the NBT reduction by both live GBS and GBS-stimulated PMN. Surfactant was peroxidized by reactive oxygen species (ROS) from both GBS and GBS-stimulated PMN in a time-dependent manner. Vitamin E significantly reduced the peroxidation level of surfactant in both cases. Surfactant peroxidation was associated with a reduction in the number of live bacteria. The biophysical activity of Curosurf was impaired by GBS-stimulated PMN, as reflected by increased minimum surface tension during cyclic compression. These findings indicate that Curosurf undergoes LPO by ROS produced by GBS and/or PMN. We speculate that exogenous surfactant preparations should be supplemented with vitamin E or another antioxidant, when given to infants with GBS pneumonia.
Insights
Group B streptococci (GBS) pneumonia in infants can impair surfactant therapy. Antioxidants like vitamin E may protect surfactant from damage caused by reactive oxygen species from GBS and immune cells.
Area of Science:
- Neonatal Medicine
- Pulmonology
- Biochemistry
Background:
- Group B streptococci (GBS) are a common cause of pneumonia in newborns.
- Polymorphonuclear leukocytes (PMN) infiltrate the lungs during GBS pneumonia.
- Surfactant therapy is crucial for managing respiratory distress in affected infants.
Purpose of the Study:
- To investigate the interaction between GBS, GBS-stimulated PMN, and the surfactant preparation Curosurf in vitro.
- To assess the impact of reactive oxygen species (ROS) on surfactant function and integrity.
- To evaluate the potential protective role of antioxidants against surfactant peroxidation.
Main Methods:
- Measurement of superoxide production using the nitroblue tetrazolium (NBT) test.
- Quantification of lipid peroxidation (LPO) via malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE) assays.
- Assessment of GBS growth in surfactant and its relation to LPO.
- Evaluation of surfactant activity using a pulsating bubble surfactometer.
Main Results:
- Curosurf reduced NBT reduction by both GBS and GBS-stimulated PMN.
- Surfactant underwent time-dependent peroxidation by ROS from GBS and PMN.
- Vitamin E significantly decreased surfactant peroxidation.
- Surfactant peroxidation correlated with a reduction in viable GBS.
- GBS-stimulated PMN impaired Curosurf's biophysical activity, increasing minimum surface tension.
Conclusions:
- Exogenous surfactant undergoes lipid peroxidation due to ROS generated by GBS and PMN.
- Vitamin E effectively mitigates surfactant peroxidation in this in vitro model.
- Supplementation of exogenous surfactant with vitamin E or other antioxidants is recommended for infants with GBS pneumonia.