Abstract
BackgroundLung 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.MethodsMacrophage 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 discussionSeven 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.
Highlights
Immaturity of the lungs due to preterm birth is one of the most significant complications affecting neonatal mortality
At birth there was no significant difference in body weight between groups (p = 0.09); after 7 days of hyperoxia exposure body weight was decreased by 18% compared to normoxia-exposed offspring (4.37 ± 0.12 g vs. 3.57 ± 0.01 g, p < 0.001; Figure 1A)
Hyperoxia resulted in a 17% increase in mean linear intercept (MLI) (80.9 ± 2.1 μm vs. 94.6 ± 2.4 μm, p < 0.05; Figure 1B), a 6% decrease in percentage tissue
Summary
Immaturity of the lungs due to preterm birth is one of the most significant complications affecting neonatal mortality. As preterm infants with respiratory distress are born with lungs at an anatomical stage not yet conducive to gas exchange, routine care practices include mechanical ventilation and oxygen supplementation. These lifesaving interventions can cause permanent damage to the developing lung, resulting in a chronic lung disease termed. Delivery of high concentrations of oxygen to neonatal animals is widely used to investigate the basis of arrested alveolar development associated with BPD in preterm infants [5,6]. Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Macrophages are traditionally associated with the propagation of inflammatory insults, increased appreciation of their diversity has revealed essential functions in development and regeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
