Spontaneous tumor cytolysis mediated by inflammatory neutrophils:
dependence upon divalent cations and reduced oxygen intermediates
A Lichtenstein
The role of divalent cations and reactive products of the respiratory burst
were investigated in spontaneous tumor lysis mediated by inflammatory
neutrophils (PMNs). Murine peritoneal PMNs, obtained five hours after
intraperitoneal injection of bacteria, conjugated and lysed teratocarcinoma
cells in chromium release and single-cell cytotoxicity assays. The presence
of extracellular magnesium was required and was sufficient for tumor cell
binding to PMNs. Postbinding lytic events depended upon the simultaneous
presence of extracellular calcium and magnesium. Catalase and superoxide
dismutase inhibited postbinding lytic events, indicating that production of
reduced oxygen moieties was important. Scavengers of hydroxyl radicals
could inhibit tumor cell binding, but none could affect postbinding lytic
events. Neither could inhibitors of myeloperoxidase decrease tumor lysis.
The ability of conjugating PMNs to lyse their bound targets correlated with
their reduction of nitro blue tetrazolium (NBT). Optimal concentrations of
phorbol myristate acetate (PMA) markedly increased the NBT positivity of
PMNs and the killing of bound tumor cells. Even with optimal stimulation of
the respiratory burst, however, there was still a significant number (19%)
of bound targets that escaped lysis, suggesting active resistance to
oxygen-mediated tumor cell injury.
Volume 67,
Issue 3,
pp. 657-665,
03/01/1986
Copyright © 1986 by The American Society of Hematology
