Antibody-Mediated Tumor Cytotoxicity of Microglia

• Published in: Pathobiology (Basel) Vol. 59; no. 4; pp. 254 - 258
• Main Authors: Sutter, S., Hekmat, A., Luckenbach, G.A.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 1991
• Subjects: Animals; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Astrocytoma - immunology; Humans; Macrophages as Tumor Cytotoxic Effector Cells; Neuroglia - immunology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - immunology; Tumor Cells, Cultured - immunology; Tumor Cells, Cultured - pathology; Tumor Cells, Cultured - physiology; Antibody-mediated cytotoxicity; Glioma; EGF receptors; Microglia
• ISBN: 3805554087; 9783805554084
• ISSN: 1015-2008; 1423-0291
• DOI: 10.1159/000163657

The status of microglial cells as potent effector cells in antibody-mediated tumor cytotoxicity (ADCC) could be established. Microglia (≧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-α 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.