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Human recombinant macrophage colony stimulating factor activates murine Kupffer cells to a cytotoxic state
S A Curley1, M S Roh, E Kleinerman
1Department of General Surgery, University of Texas M.D. Anderson Cancer Center, Houston.
Abstract:
Activated macrophages mediate cytotoxicity against tumor targets and thus may modulate development and growth of metastatic tumor cells. Macrophage colony stimulating factor (M-CSF) has a potential role in activating mature macrophages to a cytotoxic state. We employed a murine Kupffer cell (KC) model of cytotoxicity against a tumor necrosis factor (TNF) - sensitive murine colon adenocarcinoma cell line (MCA26) to evaluate the ability of recombinant human M-CSF (rhM-CSF) 1) to act alone as a KC-activating agent and 2) to enhance KC cytotoxicity against MCA26 cells in association with known macrophage activating compounds. rhM-CSF produced a dose-dependent increase in TNF release by KC in vitro with a parallel increase in MCA26 killing. KC activated by rhM-CSF produced less TNF and concomitantly demonstrated a lower cytotoxicity against MCA26 cells when compared with KC activated by gamma interferon (gamma IFN) with or without lipopolysaccharide (LPS). M-CSF did not act in a synergistic fashion with gamma IFN and LPS to increase TNF secretion or cytotoxicity against MCA26 cells. rhM-CSF thus acts as a single agent capable of activating murine KC to a cytotoxic state but does not cooperate with classical priming/triggering signals to achieve KC activation.
Insights
Macrophage colony stimulating factor (M-CSF) activates macrophages to kill tumor cells. However, M-CSF did not enhance the tumor-killing ability of macrophages when combined with other activating compounds.
Area of Science:
- Immunology
- Cancer Biology
Background:
- Activated macrophages are crucial for tumor cell cytotoxicity.
- Macrophage colony stimulating factor (M-CSF) may activate macrophages against tumors.
Purpose of the Study:
- To evaluate recombinant human M-CSF (rhM-CSF) as a Kupffer cell (KC) activator.
- To assess rhM-CSF's ability to enhance KC cytotoxicity with other compounds.
Main Methods:
- Utilized a murine KC model against a colon adenocarcinoma cell line (MCA26).
- Measured TNF release and MCA26 cell killing in response to rhM-CSF, gamma interferon (γIFN), and lipopolysaccharide (LPS).
Main Results:
- rhM-CSF dose-dependently increased TNF release and cytotoxicity.
- rhM-CSF-activated KCs showed lower cytotoxicity compared to γIFN/LPS-activated KCs.
- rhM-CSF did not synergize with γIFN and LPS for enhanced TNF secretion or cytotoxicity.
Conclusions:
- rhM-CSF alone can activate murine KCs to a cytotoxic state.
- rhM-CSF does not cooperate with classical priming/triggering signals for KC activation.