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Surfactant therapy of newborn rabbits impairs lung macrophage bactericidal activity
M P Sherman1, J B D'Ambola, E E Aeberhard
1Department of Pediatrics, University of California, Los Angeles 90024.
Abstract:
Because in vitro studies indicate that pulmonary alveolar macrophages (PAM's) filled with phospholipid vesicles have depressed microbicidal capacity, we tested the intrapulmonary bactericidal activity of newborn PAM's after surfactant treatment. Term newborn rabbits received intratracheally either homologous surfactant or one of two artificial phospholipid vesicle preparations followed by pulmonary aerosol infection with group B streptococci (GBS). Four hours after lung infection, phagocytic killing of GBS was reduced by 70-90% in animals treated with the homologous and one of the artificial surfactants compared with untreated animals or animals that received intrapulmonary injections of the surfactant vehicle (P less than 0.02). The other artificial phospholipid preparation decreased intrapulmonary inactivation of GBS by 30-40% compared with the controls. The phospholipid vesicles in the three preparations were avidly ingested and processed by newborn PAM's. The diminished in vivo killing of GBS was not attributed to decreased viability or phagocytic behavior of the PAM's toward GBS. The bactericidal defect that was evident in the newborn PAM's appeared related to the uptake of large phospholipid vesicles in the preparations rather than to the phospholipid content of the surfactants themselves. When in vitro conditions that stimulated the alveolar environment were used, the natural surfactant preparation promoted GBS proliferation, whereas the artificial preparations did not. Our findings indicate that surfactant administration reduces the bactericidal activity of neonatal PAM's. We conclude that additional investigations are needed to ascertain the effect of surfactant replacement therapy on lost defenses of the lung.
Insights
Surfactant treatment impairs the ability of newborn pulmonary alveolar macrophages (PAMs) to kill bacteria. This effect is linked to the uptake of phospholipid vesicles, potentially impacting lung defenses in neonates.
Area of Science:
- Neonatal immunology
- Pulmonary medicine
- Microbiology
Background:
- In vitro studies suggest phospholipid-laden pulmonary alveolar macrophages (PAMs) exhibit reduced microbicidal capacity.
- Neonatal lung infections pose significant health risks, necessitating understanding of immune defenses.
Purpose of the Study:
- To evaluate the intrapulmonary bactericidal activity of newborn PAMs following surfactant administration.
- To determine the impact of homologous and artificial surfactant preparations on bacterial clearance in vivo.
Main Methods:
- Term newborn rabbits were intratracheally treated with surfactant (homologous or artificial) or vehicle.
- Animals were subsequently infected with group B streptococci (GBS) via aerosol.
- Bactericidal activity was assessed 4 hours post-infection by quantifying GBS killing.
Main Results:
- Surfactant treatment (homologous and one artificial preparation) significantly reduced GBS killing by 70-90% (P < 0.02).
- Another artificial preparation showed a 30-40% reduction in GBS inactivation.
- Impaired bacterial killing was attributed to phospholipid vesicle uptake by PAMs, not altered PAM viability or phagocytosis.
Conclusions:
- Surfactant administration diminishes the bactericidal activity of neonatal PAMs.
- The uptake of large phospholipid vesicles, rather than phospholipid content, appears responsible for the observed defect.
- Further research is crucial to understand the implications of surfactant replacement therapy on neonatal lung defense mechanisms.