Role of macrophages in fetal development and perinatal disorders

In the fetus and the neonate, altered macrophage function has been implicated not only in inflammatory disorders but also in developmental abnormalities marked by altered onset, interruption, or imbalance of key structural changes. The developmental role of macrophages were first noted nearly a century ago, at about the same time when these cells were being identified as central effectors in phagocytosis and elimination of microbes. Since that time, we have made considerable progress in understanding the diverse roles that these cells play in both physiology and disease. Here, we review the role of fetal and neonatal macrophages in immune surveillance, innate immunity, homeostasis, tissue remodeling, angiogenesis, and repair of damaged tissues. We also discuss the possibility of therapeutic manipulation of the relative abundance and activation status of macrophage subsets in various diseases. This article combines peer-reviewed evidence from our own studies with results of an extensive literature search in the databases PubMed, EMBASE, and Scopus. IMPACT: We have reviewed the structure, differentiation, and classification of macrophages in the neonatal period. Neonatal macrophages are derived from embryonic, hepatic, and bone marrow precursors. Macrophages play major roles in tissue homeostasis, innate immunity, inflammation, tissue repair, angiogenesis, and apoptosis of various cellular lineages in various infectious and inflammatory disorders. Macrophages and related inflammatory mediators could be important therapeutic targets in several neonatal diseases.