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The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure
Insights
Colony-Stimulating Factor-1 (CSF-1) did not rescue lung development defects caused by neonatal hyperoxia. While CSF-1 increased macrophage numbers, it did not improve lung structure or function in this model.
Area of Science:
- Neonatal physiology and respiratory medicine
- Immunology and cellular biology
- Developmental biology
Background:
- Preterm birth leads to lung immaturity, a major neonatal health concern.
- Supplemental oxygen, while crucial for respiratory distress, can harm alveolar development.
- Macrophages, once seen as inflammatory, are now recognized for vital roles in development and repair.
Purpose of the Study:
- To investigate if macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) can protect or rescue lung development in a neonatal hyperoxia model.
- To explore the potential of CSF-1 in promoting macrophages essential for alveologenesis.
Main Methods:
- Neonatal mice were exposed to normoxia or hyperoxia (65% oxygen).
- CSF-1 or vehicle was administered in two regimes: post-hyperoxia (P7-11) or concurrently with hyperoxia (P1-5).
- Lung structure, function, and macrophage populations were assessed using morphometry, plethysmography, and flow cytometry.
Main Results:
- Seven days of hyperoxia reduced body weight and perturbed lung structure/function.
- In the post-hyperoxia treatment regime, CSF-1 increased macrophage numbers but did not rescue growth or lung structure.
- In the concurrent treatment regime, CSF-1 did not impact initial growth or macrophage numbers and did not rescue adult lung function.
Conclusions:
- CSF-1 administration did not rescue hyperoxia-induced growth and lung defects in this neonatal mouse model.
- Increased CSF-1 receptor (CSF-1R)+ macrophages were not associated with exacerbated lung injury.
- Further research into the trophic functions of macrophages is needed to explore their modulation for promoting lung maturation.
Background:
Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration.
Methods:
Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry.
Results And Discussion:
Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.
