title: An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation.
abstract: The development of the mononuclear phagocyte system requires macrophage colony-stimulating factor (CSF-1) signaling through the CSF-1 receptor (CSF1R, CD115). We examined the effect of an antibody against CSF1R on macrophage homeostasis and function using the MacGreen transgenic mouse (csf1r-enhanced green fluorescent protein) as a reporter. The administration of a novel CSF1R blocking antibody selectively reduced the CD115(+)Gr-1(neg) monocyte precursor of resident tissue macrophages. CD115(+)Gr-1(+) inflammatory monocytes were correspondingly increased, supporting the view that monocytes are a developmental series. Within tissue, the antibody almost completely depleted resident macrophage populations in the peritoneum, gastrointestinal tract, liver, kidney, and skin, but not in the lung or female reproductive organs. CSF1R blockade reduced the numbers of tumor-associated macrophages in syngeneic tumor models, suggesting that these cells are resident type macrophages. Conversely, it had no effect on inflammatory monocyte recruitment in models, including lipopolysaccharide-induced lung inflammation, wound healing, peritonitis, and severe acute graft-versus-host disease. Depletion of resident tissue macrophages from bone marrow transplantation recipients actually resulted in accelerated pathology and exaggerated donor T-cell activation. The data indicate that CSF1R signaling is required only for the maturation and replacement of resident-type monocytes and tissue macrophages, and is not required for monocyte production or inflammatory function.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Kelli P A
authors.initials: KP
authors.lastname: MacDonald
authors.forename: James S
authors.initials: JS
authors.lastname: Palmer
authors.forename: Stephen
authors.initials: S
authors.lastname: Cronau
authors.forename: Elke
authors.initials: E
authors.lastname: Seppanen
authors.forename: Stuart
authors.initials: S
authors.lastname: Olver
authors.forename: Neil C
authors.initials: NC
authors.lastname: Raffelt
authors.forename: Rachel
authors.initials: R
authors.lastname: Kuns
authors.forename: Allison R
authors.initials: AR
authors.lastname: Pettit
authors.forename: Andrew
authors.initials: A
authors.lastname: Clouston
authors.forename: Brandon
authors.initials: B
authors.lastname: Wainwright
authors.forename: Dan
authors.initials: D
authors.lastname: Branstetter
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Smith
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Paxton
authors.forename: Douglas Pat
authors.initials: DP
authors.lastname: Cerretti
authors.forename: Lynn
authors.initials: L
authors.lastname: Bonham
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019891:Leukopoiesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000145:classification / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051381:Rats; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016186:Receptor, Macrophage Colony-Stimulating Factor