title: Characterisation of a novel Fc conjugate of macrophage colony-stimulating factor.
abstract: We have produced an Fc conjugate of colony-stimulating factor (CSF) 1 with an improved circulating half-life. CSF1-Fc retained its macrophage growth-promoting activity, and did not induce proinflammatory cytokines in vitro. Treatment with CSF1-Fc did not produce adverse effects in mice or pigs. The impact of CSF1-Fc was examined using the Csf1r-enhanced green fluorescent protein (EGFP) reporter gene in MacGreen mice. Administration of CSF1-Fc to mice drove extensive infiltration of all tissues by Csf1r-EGFP positive macrophages. The main consequence was hepatosplenomegaly, associated with proliferation of hepatocytes. Expression profiles of the liver indicated that infiltrating macrophages produced candidate mediators of hepatocyte proliferation including urokinase, tumor necrosis factor, and interleukin 6. CSF1-Fc also promoted osteoclastogenesis and produced pleiotropic effects on other organ systems, notably the testis, where CSF1-dependent macrophages have been implicated in homeostasis. However, it did not affect other putative CSF1 targets, notably intestine, where Paneth cell numbers and villus architecture were unchanged. CSF1 has therapeutic potential in regenerative medicine in multiple organs. We suggest that the CSF1-Fc conjugate retains this potential, and may permit daily delivery by injection rather than continuous infusion required for the core molecule.
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Deborah J
authors: DJ
authors: Gow
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Kristin A
authors: KA
authors: Sauter
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Clare
authors: C
authors: Pridans
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Lindsey
authors: L
authors: Moffat
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Anuj
authors: A
authors: Sehgal
authors: The University of Edinburgh/MRC centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh, UK.
authors: Ben M
authors: BM
authors: Stutchfield
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Sobia
authors: S
authors: Raza
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Philippa M
authors: PM
authors: Beard
authors: The University of Edinburgh/MRC Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, UK.
authors: Yi Ting
authors: YT
authors: Tsai
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Graeme
authors: G
authors: Bainbridge
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Pamela L
authors: PL
authors: Boner
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Greg
authors: G
authors: Fici
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: David
authors: D
authors: Garcia-Tapia
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Roger A
authors: RA
authors: Martin
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Theodore
authors: T
authors: Oliphant
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: John A
authors: JA
authors: Shelly
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Raksha
authors: R
authors: Tiwari
authors: Zoetis, Kalamazoo, Michigan, USA.
authors: Thomas L
authors: TL
authors: Wilson
authors: The University of Edinburgh/MRC Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, UK.
authors: Lee B
authors: LB
authors: Smith
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: Neil A
authors: NA
authors: Mabbott
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, UK.
authors: David A
authors: DA
authors: Hume
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation; D003412:Cricetulus; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006207:Half-Life; D022781:Hepatocytes / Q000378:metabolism*; D006529:Hepatomegaly / Q000139:chemically induced*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D044968:Regenerative Medicine; D013163:Splenomegaly / Q000139:chemically induced*; D013552:Swine / Q000276:immunology*
chemical_list: D007141:Immunoglobulin Fc Fragments; D016173:Macrophage Colony-Stimulating Factor