Related Experiment Video
Updated: Oct 4, 2026
Lentiviral Vector Preparation for Efficient Gene and MicroRNA Modulation of Peritoneal Cavity Tissue-Resident Macrophages In Vivo in Mice
Published on: February 16, 2024
Effects of murine leukemia virus env gene proteins on macrophage-mediated cytotoxicity in vitro
1Division of Biology, Kansas State University, Manhattan 66506, USA.
Abstract:
F5b Tumor cells were incubated with concentrated culture supernatants taken from cells resistant (F5m) or sensitive (F5b) to contact-dependent macrophage cytotoxicity. Macrophage cell line B6MP102 and murine peritoneal macrophages killed targets incubated with supernatants taken from sensitive cells but poorly killed cells incubated in supernatants isolated from resistant cells. Membranes from cells resistant to macrophage killing, F5m, were fused into F5b cells. The fused F5b cells were killed significantly less than F5b cells fused with F5b cell membranes or untreated F5b cells. The decreased killing of F5b cells corresponded to increased concentrations of gp70(a) molecules on F5b cells. Affinity purified gp70(a) was added to cytotoxicity assays but failed to inhibit macrophage cytotoxicity. P15E molecules were detectable on both F5b and F5m cells. In addition, a synthetic peptide found to exhibit the inhibitory properties of p15E was added to cytotoxicity assays. P15E synthetic peptide also did not inhibit macrophage cytotoxicity. Therefore, env gene proteins of murine leukemia virus do not appear responsible for inducing tumor cell resistance to activated macrophage contact-dependent cytotoxicity.
Insights
Tumor cells resistant to macrophage killing were identified. Proteins like gp70(a) and P15E on resistant cells did not explain this resistance to contact-dependent cytotoxicity.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Contact-dependent cytotoxicity is a mechanism by which macrophages eliminate tumor cells.
- Tumor cell resistance to this killing mechanism is a significant challenge in cancer therapy.
Purpose of the Study:
- To investigate the molecular basis of tumor cell resistance to contact-dependent macrophage cytotoxicity.
- To determine if specific murine leukemia virus (MLV) env gene proteins contribute to this resistance.
Main Methods:
- Incubation of F5b tumor cells with culture supernatants from resistant (F5m) and sensitive (F5b) cells.
- Fusion of membranes from resistant F5m cells into sensitive F5b cells.
- Assessment of macrophage killing of modified F5b cells.
- Analysis of gp70(a) and P15E molecule expression and functional inhibition assays.
Main Results:
- Supernatants from resistant cells conferred resistance to macrophage killing.
- Fusing membranes from resistant cells into sensitive cells reduced their susceptibility to killing.
- Increased gp70(a) concentrations correlated with decreased F5b cell killing, but purified gp70(a) did not inhibit cytotoxicity.
- P15E molecules and a synthetic P15E peptide did not inhibit macrophage cytotoxicity.
Conclusions:
- Tumor cell resistance to contact-dependent macrophage cytotoxicity is mediated by factors present in resistant cell-derived supernatants and membranes.
- gp70(a) and P15E, proteins encoded by MLV env genes, do not appear to be responsible for inducing this resistance.
