title: Inhibition of colony-stimulating factor-1 activity by monoclonal antibodies to the human CSF-1 receptor.
abstract: Four of 12 monoclonal antibodies (MoAbs) directed to different epitopes in the extracellular domain of the human colony-stimulating factor-1 receptor (CSF-1R, the c-fms proto-oncogene product) specifically inhibit CSF-1 binding to receptor-bearing cells. All four antibodies abrogated CSF-1-dependent colony formation by human bone marrow-derived macrophage precursors and by mouse NIH-3T3 cells expressing a transduced human c-fms gene. In addition, one of these antibodies (designated MoAb 2-4A5) interfered with the ligand-independent proliferation of NIH-3T3 cells transformed by an oncogenic, mutant c-fms allele. Unlike CSF-1 itself, neither MoAb 2-4A5 nor the other three inhibitory antibodies (MoAbs 12-2D6, 12-3A1, and 12-3A3) induced CSF-1R internalization or degradation. These antibodies should prove useful not only for identifying and quantitating CSF-1R on receptor-bearing cells but for abrogating specific receptor signals that govern the proliferation and survival of human mononuclear phagocytes.
authors.affiliation: Howard Hughes Medical Institute, St Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: C J
authors.initials: CJ
authors.lastname: Sherr
authors.forename: R A
authors.initials: RA
authors.lastname: Ashmun
authors.forename: J R
authors.initials: JR
authors.lastname: Downing
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: S G
authors.initials: SG
authors.lastname: Quan
authors.forename: D W
authors.initials: DW
authors.lastname: Golde
authors.forename: M F
authors.initials: MF
authors.lastname: Roussel
mesh_terms: D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor
chemical_list: D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor