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Activated macrophages use different cytolytic mechanisms to lyse a virally infected or a tumor target
P A LeBlanc1, L S Heath, H D Um
1Department of Microbiology, University of Alabama, Tuscaloosa 35487-0334.
Abstract:
Murine bone-marrow-culture-derived-macrophages can be differentially activated to lyse either vesicular stomatitis virus infected BALB/c3T3 cells or the tumor target P815. Macrophages were activated in a manner so that they could lyse both targets. The ability of this activated population to lyse either target type was differentially inhibited by varying the assay conditions. The lysis of P815 targets was more sensitive to inhibition by the proteinase inhibitor N-p-tosyl-L-lysine chloromethyl ketone than was the lysis of virally infected cells. On the other hand, reduction of the concentration of glucose in the assay medium, which inhibits the production of oxygen metabolites by the hexose monophosphate shunt, or the addition of anti-tumor necrosis factor (anti-TNF) serum were able to decrease the lysis of virally infected targets but not P815 targets. Thus, the observed differences in the lysis of these two targets were due to both the activation state of the macrophages and the differential susceptibility of the targets to different effector mechanisms.
Insights
Macrophages can be activated to target both virus-infected cells and tumor cells. Different conditions selectively inhibited the lysis of these distinct targets, revealing unique macrophage effector mechanisms.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages exhibit diverse activation states.
- Macrophages can be differentiated to target specific cells, including virally infected cells and tumor cells.
Purpose of the Study:
- To investigate the differential activation and effector mechanisms of macrophages against distinct target cells.
- To understand how assay conditions influence macrophage-mediated lysis of virus-infected cells versus tumor cells.
Main Methods:
- Murine bone-marrow-derived macrophages were activated to lyse both vesicular stomatitis virus-infected BALB/c3T3 cells and P815 tumor cells.
- Assay conditions were varied, including the use of a proteinase inhibitor (N-p-tosyl-L-lysine chloromethyl ketone), glucose concentration reduction, and anti-tumor necrosis factor (anti-TNF) serum addition.
Main Results:
- Activated macrophages demonstrated the capacity to lyse both viral and tumor targets.
- P815 target lysis was more sensitive to the proteinase inhibitor than viral target lysis.
- Reduced glucose or anti-TNF serum inhibited viral target lysis but not P815 target lysis.
Conclusions:
- Macrophage effector mechanisms differ based on target cell type and activation state.
- Differential susceptibility of targets to specific inhibitory conditions highlights distinct cytotoxic pathways.