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Immunol Cell Biol. 2012 Apr;90(4):429-40. doi: 10.1038/icb.2011.58. Epub 2011 Jul 5.

Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in homeostasis and inflammation.

Author information

  • 1Arthritis and Inflammation Research Centre, Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia. jlenzo@unimelb.edu.au

Abstract

There is recent interest in the role of monocyte/macrophage subpopulations in pathology. How the hemopoietic growth factors, macrophage-colony stimulating factor (M-CSF or CSF-1) and granulocyte macrophage (GM)-CSF, regulate their in vivo development and function is unclear. A comparison is made here on the effect of CSF-1 receptor (CSF-1R) and GM-CSF blockade/depletion on such subpopulations, both in the steady state and during inflammation. In the steady state, administration of neutralizing anti-CSF-1R monoclonal antibody (mAb) rapidly (within 3-4 days) lowered, specifically, the number of the more mature Ly6C(lo) peripheral blood murine monocyte population and resident peritoneal macrophages; it also reduced the accumulation of murine exudate (Ly6C(lo)) macrophages in two peritonitis models and alveolar macrophages in lung inflammation, consistent with a non-redundant role for CSF-1 (or interleukin-34) in certain inflammatory reactions. A neutralizing mAb to GM-CSF also reduced inflammatory macrophage numbers during antigen-induced peritonitis and lung inflammation. In GM-CSF gene-deficient mice, a detailed kinetic analysis of monocyte/macrophage and neutrophil dynamics in antigen-induced peritonitis suggested that GM-CSF was acting, in part, systemically to maintain the inflammatory reaction. A model is proposed in which CSF-1R signaling controls the development of the macrophage lineage at a relatively late stage under steady state conditions and during certain inflammatory reactions, whereas in inflammation, GM-CSF can be required to maintain the response by contributing to the prolonged extravasation of immature monocytes and neutrophils. A correlation has been observed between macrophage numbers and the severity of certain inflammatory conditions, and it could be that CSF-1 and GM-CSF contribute to the control of these numbers in the ways proposed.

PMID:
21727904
[PubMed - indexed for MEDLINE]
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