Abstract
Bronchopulmonary dysplasia (BPD) is characterized by abnormal alveolar septation and microvascular development. Certain types of monocytes and macrophages have been implicated in epithelial growth and angiogenesis, while others play a role in immune defense and inflammation.
Aims: To investigate whether monocyte/macrophage profiles and their products correlate with BPD development.
Methods: We investigated lungs of neonatal mice and tracheal aspirates (TAs) from preterm born infants.
Results: We found that M2-MDSC like monocytes are abundantly present in the lungs of neonatal mice. These monocytes also showed high expression of proangiogenic genes (a.o. EMMPRIN, ENA78, GDF15, VEGFR2 and IGF-1) and strong immune suppressive capacity in vitro, supporting a role in maintaining tissue homeostasis and lung growth. Upon repetitive exposure to LPS the monocytes lost their M2-profile and suppressive capacity and upregulated inflammatory markers (IL-8, IL-1b and IL-6 but not TNFa).
We also found monocytes/macrophages in TAs from preterm born infants. Proteome profiling these TAs revealed high concentrations of both M2 and inflammatory monocyte/macrophage derived factors and angiogenic mediators. Addition of TAs to pericyte-endothelial cell co-cultures either enhanced or inhibited angiogenesis. Luminex analysis of TAs of preterm infants with (n=22) and without (n=23) BPD showed significant lower concentrations of the angiogenic factors EMMPRIN, ENA78, MCP1, GDF15, TNF-α, Angiopoietin-1, -2 and HGF in those infants who developed BPD.
Conclusion: Our data indicate that monocyte/macrophage profiles in TAs of premature children correlate with BPD development and may be used to identify new preventive or therapeutic targets.
- Copyright ©the authors 2016
