From proliferation to proliferation: monocyte lineage comes full circle

Semin Immunopathol (2014) 36:137148 DOI 10.1007/s00281-013-0409-1

REVIEW

From proliferation to proliferation: monocyte lineage comes full circle

Filip K. Swirski & Ingo Hilgendorf & Clinton S. Robbins

Received: 4 November 2013 /Accepted: 25 November 2013 /Published online: 17 January 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Monocytes are mononuclear circulating phagocytes that originate in the bone marrow and give rise to macrophages in peripheral tissue. For decades, our understanding of monocyte lineage was bound to a stepwise model that favored an inverse relationship between cellular proliferation and differentiation. Sophisticated molecular and surgical cell tracking tools have transformed our thinking about monocyte topo-ontogeny and function. Here, we discuss how recent studies focusing on progenitor proliferation and differentiation, monocyte mobilization and recruitment, and macrophage differentiation and proliferation are reshaping knowledge of monocyte lineage in steady state and disease.

Keywords Monocyte . Hematopoiesis . Macrophage .

Proliferation . Atherosclerosis

Introduction

For years, monocytes were viewed simply as transitional cells, fated to give rise to either macrophages or dendritic cells depending on tissue context. With the discovery of functionally heterogeneous monocyte subsets in several species, it is clear that monocyte participation in the immune response

extends beyond differentiation. Several populations of increasingly restricted myeloid and monocyte progenitors have been identified in the bone marrow. Adding to the complexity, recent evidence points to embryonic, rather than hematopoietic, origins for macrophages in many tissues. This finding has led to the realization that macrophage renewal often relies on local proliferation rather than monocyte recruitment. Our own research demonstrates that monocyte-derived macrophages also self-renew via mechanisms that are distinct from those facilitating monocyte generation and recruitment. Here, we discuss the latest contributions to our understanding of monocytemacrophage lineage commitment in homeostasis and during inflammation. We will focus on the monocytemacrophage lineage in cardiovascular disease, the major cause of death worldwide [1] but will also draw from other literature to provide broader context. A graphical representation of our discussion is found in Fig. 1.

Progenitor proliferation and differentiation

In the healthy adult, monocytes arise through the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPC) in the bone marrow. The sequential differentiation that links the multipotent, self-renewing hematopoietic stem cell (HSC) to the terminally-differentiated and non-renewing monocyte involves a series of distinct intermediate populations...