Inhibition of colony-stimulating factor-1 activity by monoclonal antibodies to the human CSF-1 receptor.
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.
Sherr
C J
CJ
Howard Hughes Medical Institute, St Jude Children's Research Hospital, Memphis, TN 38105.
Ashmun
R A
RA
Downing
J R
JR
Ohtsuka
M
M
Quan
S G
SG
Golde
D W
DW
Roussel
M F
MF
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
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