Proliferation of monocytes and macrophages in homeostasis, infection, injury, and disease

Monocytes (Mo) and macrophages (M) 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 M-phi are end-stage cells that do not proliferate and that M-phi accumulation in tissues is the result of infiltration of Mo from the blood and subsequent differentiation to M-phi. However, reports from the early 1900s to the present describe evidence of Mo and M-phi proliferation in different tissues and contexts. The purpose of this review is to summarize both historical and current evidence for the contribution of M-phi proliferation to their accumulation in different tissues during homeostasis, infection, injury, and disease. M-phi proliferate M-phi 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 human. M-phi 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 M-phi proliferating in other inflammatory contexts (e.g. nematode infection, acetaminophen liver injury) and during homeostasis. The pathways involved in stimulating M-phi proliferation also may be context dependent, with different cytokines and transcription factors implicated in different studies. Although M-phi are known to proliferate in health, injury, and disease, much remains to be learned about the regulation of M-phi proliferation in different contexts and its impact on the homeostasis, injury, and repair of different organs and tissues. .