The spatial and developmental relationships in the macrophage family.

A classic study in 1968 proposed that bone marrow-dwelling promonocytes differentiate to monocytes, which then intravasate, circulate, and, on tissue entry, differentiate to sessile macrophages. Since then, understanding of the macrophage family relationship has undergone substantial enhancement and occasional revision. It is currently recognized that in addition to their role in the bone marrow, hematopoietic progenitors circulate and give rise to their descendants in extramedullary niches. Monocytes, of which there are several subsets, are not merely circulating macrophage precursors but participate in the immune response in their own right. Macrophages are highly heterogeneous and, as recent studies indicate, can arise in the absence of a monocyte intermediate. These spatial and developmental relationships reveal a complex interactive network and underscore the importance of context in evaluating biological systems. The observations have significant implications for how we image, target, and treat disease.