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Cytolytic activity of macrophages isolated from primary murine sarcoma virus (MSV)-induced tumors
Abstract:
Macrophages isolated from regressing or progressing tumors induced by murine sarcoma virus (MSV) were tested for cytolytic activity in a 18-h 51Cr release assay. Macrophages from the tumors of mice injected 14 days earlier with stocks of MSV-producing regressor or progressor tumors had comparable levels of cytotoxicity. However, macrophages from the progressively growing tumors, 50--65 days after the inoculation with the progressor virus, had lower levels of cytotoxicity than those from the regressing tumors (day 14). On the other hand, macrophages from progressively growing MSV tumors (day 14) in nude mice had little or no detectable cytolytic activity. In a fractionation study, using the 1-g velocity sedimentation technique, cells from regressing tumors (day 14) showed at least two peaks of cytolytic activity, one at about 4 mm/h and another at 6--7 mm/h. In contrast, none of the cell fractions of tumors from nude mice (day 14) showed cytolytic activity. Since bacterial lipopolysaccharide (LPS) has been shown to augment the cytolytic activity of primed macrophages, its effect on cells from MSV tumors was evaluated. Cytolytic activity of the cells from regressing or progr-ssing tumors that had pre-existing cytolytic activity was augmented by the addition of LPS during the assay period, but LPS treatment did not activate inactive fractions or change the distribution patterns of the cytolytic activity in fractions from 1-g velocity sedimentation.
Insights
Macrophages from regressing tumors show higher cytolytic activity than those from progressing tumors. Bacterial lipopolysaccharide (LPS) enhances this activity but cannot activate non-cytolytic cells.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Macrophages play a crucial role in anti-tumor immunity.
- Tumor progression can be influenced by the immune microenvironment.
- Murine sarcoma virus (MSV) provides a model for studying tumor-host interactions.
Purpose of the Study:
- To investigate the cytolytic activity of macrophages in murine sarcoma virus (MSV)-induced tumors.
- To compare macrophage activity in regressing versus progressing tumors.
- To assess the effect of bacterial lipopolysaccharide (LPS) on macrophage cytolytic function in this model.
Main Methods:
- Isolation of macrophages from MSV-induced tumors at different time points.
- Chromium-51 (51Cr) release assay to measure cytolytic activity.
- 1-g velocity sedimentation for cell fractionation.
- Treatment with bacterial lipopolysaccharide (LPS) to evaluate its effect on cytolytic activity.
Main Results:
- Macrophages from regressing tumors exhibited comparable or higher cytolytic activity than those from early-stage progressing tumors.
- Macrophages from late-stage progressing tumors (50-65 days) showed significantly lower cytolytic activity.
- Tumor-associated macrophages from nude mice (lacking T-cell immunity) displayed minimal to no cytolytic activity.
- Velocity sedimentation revealed distinct peaks of cytolytic activity in regressing tumor macrophages, absent in nude mouse tumor macrophages.
- LPS augmented existing cytolytic activity but did not activate non-cytolytic cell fractions.
Conclusions:
- Macrophage cytolytic activity is diminished during later stages of MSV tumor progression.
- The tumor microenvironment, particularly in the absence of adaptive immunity (nude mice), impairs macrophage function.
- LPS can enhance, but not restore, impaired macrophage cytolytic capacity in MSV tumors.