Inhibition by monosaccharides of tumor associated macrophages mediated antibody dependent cell cytotoxicity to autologous tumor cells

Abstract

A number of mono- and oligosaccharides are known to inhibit direct contact mediated cytotoxicity of natural killer cells, cytotoxic T lymphocytes and macrophages. In antibody dependent cell mediated cytotoxicity (ADCC), where antibody molecules mediate target recognition, binding and lysis, the role of cell surface carbohydrates is not clearly defined. In the present paper the effects of D-mannose (D-man), N-acetylglucosamine (N-AcGlc), N-acetylgalactosamine (N-AcGal) and glucose on binding and lytic events of ADCC by the tumor associated macrophages (TAM) to autologous tumor cells (ATC) were studied. The TAM were isolated on day 3 of growth of a transplantable ascites tumor--S-180, in Swiss mice. D-man, N-AcGlc and N-AcGal when added to the assay partially inhibited ADCC at 15 mM but at 25 and 40 mM totally abrogated ADCC. Glucose marginally enhanced ADCC at 25 mM but at other concentrations partial inhibition of ADCC occurred. Preincubation of TAM with 25 mM of D-man, N--AcGlc and N-AcGal resulted in total abrogation of ADCC with significant reduction in their binding of ATC, whereas, pretreatment of ATC with the sugars produced 30-40% inhibition of lysis with marginal reduction in target binding. The inhibitory effects of D-man, N-AcGlc and N-AcGal were also observed on ADCC mediated by the peritoneal resident macrophages (RM) of Swiss mice. "Lectin-like" receptors were postulated to be present on the surface of TAM which were involved in ADCC and were inhibitable by sugars.