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The role of monocyte derived growth factors in BPD development

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 i n 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.