Antibody-mediated tumor cytotoxicity of microglia.
The status of microglial cells as potent effector cells in antibody-mediated tumor cytotoxicity (ADCC) could be established. Microglia (greater than or equal to 99.9% pure) derived from brain cortices of newborn mice were shown to lyse human tumor cell lines expressing different levels of epidermal growth factor (EGF) receptors in the presence of MAb 425, a monoclonal murine anti-primate EGF receptor antibody. MAb 425 mediates microglial ADCC (MiADCC) at concentrations as low as 10(-11) M. Antibody ligands binding unilaterally to either EGF receptors on target cells or Fc receptors on microglia have little effect on MiADCC. At 10(-10) M MAb 425, a 10(3)-fold excess of MAb 425 F(ab')2 fragments or irrelevant antibodies of identical isotype did not block MAb-425-induced MiADCC. Formation of effector-target cell contacts seems to be critical for MiADCC and MiADCC could not be inhibited by anti-tumor necrosis factor-alpha antibodies. In addition to its stimulatory effect on MiADCC, MAb 425 bound to EGF receptors exerted a microgliotrophic effect. Factor(s) derived from astrocytes enhance MiADCC.
Sutter
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Department of Immunopharmacology, E. Merck, Darmstadt, FRG.
Hekmat
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Luckenbach
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GA
D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D001254:Astrocytoma / Q000276:immunology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D009457:Neuroglia / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000473:pathology / Q000502:physiology
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors