Proliferation of Monocytes and Macrophages in Homeostasis, Infection, Injury and Disease.

Monocytes (Mo) and macrophages (Mϕ) play important roles in the function of tissues, organs, and systems of all animals, during homeostasis, infection, injury and disease. For decades, conventional wisdom has dictated that Mo and Mϕ are end-stage cells that do not proliferate and that Mϕ accumulation in tissues is the result of infiltration of Mo from the blood and subsequent differentiation to Mϕ. However, reports from the early 1900s to the present describe evidence of Mo and Mϕ proliferation in different tissues and contexts. The purpose of this review is to summarize both historical and current evidence for the contribution of Mϕ proliferation to their accumulation in different tissues during homeostasis, infection, injury and disease. Mϕ proliferate in different organs and tissues, including skin, peritoneum, lung, heart, aorta, kidney, liver, pancreas, brain, spinal cord, eye, adipose tissue and uterus and in different species including mouse, rat, rabbit and humans. Mϕ can proliferate at different stages of differentiation with infiltrating Mo-like cells proliferating in certain inflammatory contexts (e.g., skin wounding, kidney injury, bladder and liver infection) and mature resident Mϕ proliferating in other inflammatory contexts (e.g., nematode infection, acetaminophen liver injury) and during homeostasis. The pathways involved in stimulating Mϕ proliferation also may be context-dependent, with different cytokines and transcription factors implicated in different studies. Although Mϕ are known to proliferate in health, injury and disease, much remains to be learned about the regulation of Mϕ proliferation in different contexts and its impact on the homeostasis, injury and repair of different organs and tissues.