Published online Nov 27, 2015. doi: 10.5411/wji.v5.i3.131
Peer-review started: July 14, 2015
First decision: July 31, 2015
Revised: October 10, 2015
Accepted: October 23, 2015
Article in press: October 27, 2015
Published online: November 27, 2015
The origin of macrophages has been considered since several decades to be a continuum from bone marrow (BM) to tissue via monocytes as precursors. The development of new tools such as genetic lineage tracing, parabiosis and BM chimeras changed the paradigm of macrophage origin. In steady state, most resident macrophages are of embryonic origin, whereas a monocyte origin remains prominent in pathological conditions. The findings of a proliferation of mature macrophages will oblige us to reappraise the relationship between proliferation and differentiation in macrophages. This review is based on the recent explosion of high impact articles on macrophage biology. It summarizes new data on the origin of macrophages and their self-renewal potential in steady states. While monocytes are required for intestinal macrophage development, the microglia is independent of monocyte influx and skin macrophages provide an excellent model of the balance between monocyte input and self-renewal. In addition, macrophage proliferation requires intrinsic and extrinsic factors including growth factors and cytokines. It also analyzes the impact of this new paradigm in human diseases such as athrosclerosis, cancer, infectious diseases and neurodegenerative diseases. In atherosclerosis, the finding of macrophage proliferation within the lesions will change our understanding of disease pathophysiology, this new paradigm may have therapeutical impact in the future.
Core tip: The emergence of revolutionary technologies in myeloid cell research has deeply changed the paradigm of macrophage activation. It was believed that macrophage derive from myeloid precursors via circulating monocytes. Now, we can propose that resident macrophages are of embryonic origin in steady state whereas monocytes are recruited in pathological conditions. The second strong idea was that mature macrophages are unable to proliferate; we have strong evidence that macrophages can proliferate, which is the basis of self-renewal. The consequences of these new concepts will lead us to reappraise the role of macrophages in pathologies.