Contribution of resident and recruited macrophages in vascular physiology and pathology

Macrophages are generally believed to originate entirely from the bone marrow; however, this paradigm is challenged by the discovery of yolk-sac-derived resident macrophages. Here, we provide an overview of recent advances in the ontogeny and function of resident macrophages.

Macrophage precursors from three distinct embryonic sources (yolk sac, fetal liver and bone marrow) are found to colonize various tissues via the blood circulation early during embryogenesis until shortly after birth. They differentiate into distinct long-lived resident macrophages in response to the expression of tissue-specific transcription factors. Resident macrophages are proficient at taking up tissue-specific cellular debris and consequently acquire tissue-specific imprints. They are primarily involved in homeostasis but can also support the functionality of various tissues. Under pathological settings, dysregulation of resident macrophages can promote disease progression.

Resident macrophages maintain themselves via in-situ proliferation under steady state. Following injury, bone marrow monocytes can contribute to the resident macrophage pool in adult animal. Embryonically and postnatally derived resident macrophages are similar but not identical: the former are more efficient at efferocytosis, whereas the latter are more competent at host defense. Thus, specific targeting of these two different resident macrophage populations may lead to better therapeutic strategies.