Infection of DBA/2 or C3H/HeJ mice by intraperitoneal injection of vaccinia virus elicits activated macrophages, cytolytic and cytostatic for S91-melanoma tumor cells

Abstract

Murine peritoneal macrophages harvested 3-4 days after IP injection of vaccinia virus lysed S91-melanoma tumor cells in vitro; enhanced tumoricidal activity was measured with effector macrophages prepared 5-6 days after vaccinia virus infection. Treatment of virus-elicited macrophages prepared from DBA/2 mice with anti-asialo-GM1 antiserum, anti-Thy 1.2 antiserum or anti-Iad antiserum in the presence of complement so that cells sensitized with antibodies were lysed, did not reduce the measured level of tumoricidal activity indicating that macrophages [Ia(-); asialo GM1(-)] and not natural killer cells [asialo GM1(+); Thy 1.2(+/-)] or T-cells [Thy 1.2(+)] were responsible for mediating the lysis of S91-melanoma tumor cells. When incubated with virus-elicited macrophages but not thioglycollate-elicited macrophages, the ability of S91-melanoma tumor cells. to synthesize DNA was completely blocked. The results of these experiments support the view that one aspect of antitumor immunity enhanced during immunotherapy with vaccinia virus is the activation of macrophages which have cytolytic as well as cytostatic effects on melanoma tumor cells.

Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites.

“…Although VV-elicited macrophages can lyse certain tumor targets (34), the inhibition of viral replication in both transformed and nontransformed primary cell cultures was a consequence of cytostasis, which may reflect differences in the susceptibilities of tumor cells and vitally infected cells to macrophage-derived NO. Inhibition of viral replication was observed only when activated macrophages and virus-infected target cells were cultured together.…”