Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation

• Published in: Nature communications Vol. 4; no. 1; p. 1886
• Main Authors: Davies, Luke C., Rosas, Marcela, Jenkins, Stephen J., Liao, Chia-Te, Scurr, Martin J., Brombacher, Frank, Fraser, Donald J., Allen, Judith E., Jones, Simon A., Taylor, Philip R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2013; Nature Publishing Group
• Subjects: 631/250/2504/342; 631/250/256; Animals; Antigens, Ly - metabolism; Bone Marrow Cells - pathology; Cell Lineage; Cell Proliferation; Female; Humanities and Social Sciences; Inflammation - immunology; Inflammation - pathology; Interleukin-4 - metabolism; Kinetics; Macrophage Colony-Stimulating Factor - metabolism; Macrophages - metabolism; Macrophages - pathology; Mice; Mice, Inbred C57BL; multidisciplinary; Peritonitis - immunology; Peritonitis - pathology; Receptors, Interleukin-4 - metabolism; Science; Science (multidisciplinary); Zymosan
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms2877

The general paradigm is that monocytes are recruited to sites of inflammation and terminally differentiate into macrophages. There has been no demonstration of proliferation of peripherally-derived inflammatory macrophages under physiological conditions. Here we show that proliferation of both bone marrow-derived inflammatory and tissue-resident macrophage lineage branches is a key feature of the inflammatory process with major implications for the mechanisms underlying recovery from inflammation. Both macrophage lineage branches are dependent on M-CSF during inflammation, and thus the potential for therapeutic interventions is marked. Furthermore, these observations are independent of Th2 immunity. These studies indicate that the proliferation of distinct macrophage populations provides a general mechanism for macrophage expansion at key stages during inflammation, and separate control mechanisms are implicated. Monocytes are recruited to sites of damage or infection where they differentiate into inflammatory macrophages. Here the authors demonstrate that, contrary to the prevailing model, these differentiated cells are able to proliferate at sites of inflammation.