title: Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of stimulation by CSF-1 and Interleukin 34.
abstract: Macrophage Colony Stimulating Factor (CSF-1) controls the survival, differentiation and proliferation of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, Interleukin 34 (IL-34), has been described, but its physiological role is not yet known. The domestic pig provides an alternative to traditional rodent models for evaluating potential therapeutic applications of CSF-1R agonists and antagonists. To enable such studies, we cloned and expressed active pig CSF-1. To provide a bioassay, pig CSF-1R was expressed in the factor-dependent Ba/F3 cell line. On this transfected cell line, recombinant porcine CSF-1 and human CSF-1 had identical activity. Mouse CSF-1 does not interact with the human CSF-1 receptor but was active on pig. By contrast, porcine CSF-1 was active on mouse, human, cat and dog cells. IL-34 was previously shown to be species-specific, with mouse and human proteins demonstrating limited cross-species activity. The pig CSF-1R was equally responsive to both mouse and human IL-34. Based upon the published crystal structures of CSF-1/CSF-1R and IL34/CSF-1R complexes, we discuss the molecular basis for the species specificity.
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, Scotland, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Gow
authors.forename: Valerie
authors.initials: V
authors.lastname: Garceau
authors.forename: Ronan
authors.initials: R
authors.lastname: Kapetanovic
authors.forename: David P
authors.initials: DP
authors.lastname: Sester
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Fici
authors.forename: John A
authors.initials: JA
authors.lastname: Shelly
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Wilson
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D002460:Cell Line; D003001:Cloning, Molecular; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D013045:Species Specificity; D013552:Swine
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor