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Activation process of macrophages after in vitro treatment of mouse lymphocytes with dodecylglycerol
1Department of Microbiology and Immunology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
Abstract:
Alkylglycerols, inflammation products of cancerous membrane lipids, efficiently activate macrophages. A brief in vitro treatment (30 min) of peritoneal cells (mixture of non-adherent and adherent cells) with a small amount (50 ng/ml) of synthetic dodecylglycerol (DDG) resulted in greatly enhanced Fc-receptor-mediated ingestion activity of macrophages. However, treatment of adherent cells (macrophages) alone with DDG produced no significant enhancement of macrophage ingestion activity, implying that macrophage activation requires a contribution of non-adherent cells. DDG-treated non-adherent cells were found to generate a macrophage-activating signal factor. Studies with a serum free-0.1% egg albumin-supplemented RPMI 1640 medium revealed that a serum factor is essential for macrophage activation process. Time course analysis of stepwise transfers of conditioned media of DDG-treated or untreated B cells and T cells revealed that DDG-treated B cells rapidly transmit a factor to untreated T cells which yield the ultimate macrophage-activating factor. This signal transmission among these cells for the macrophage activation process is too rapid to allow time for synthesis of inducible gene products. Thus, we hypothesized that a serum factor is modified by the pre-existing function of DDG-treated B cells and further modified by the pre-existing function of untreated T cells to yield macrophage-activating factor. This hypothesis was confirmed by the demonstration that DDG-treated splenic non-adherent cell ghosts modify a serum factor to yield macrophage-activating factor.
Insights
Synthetic dodecylglycerol (DDG) activates macrophages by engaging non-adherent cells, which produce a signal factor. This factor, along with a serum component, is then processed by B and T cells to fully activate macrophages.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Alkylglycerols are inflammation products derived from cancerous membrane lipids.
- Alkylglycerols are known to activate macrophages, key immune cells involved in host defense and inflammation.
Purpose of the Study:
- To investigate the mechanism by which synthetic dodecylglycerol (DDG) activates macrophages.
- To identify the cellular components and factors involved in DDG-mediated macrophage activation.
Main Methods:
- Peritoneal cells were treated in vitro with synthetic dodecylglycerol (DDG).
- Macrophage ingestion activity was measured via Fc-receptor-mediated phagocytosis.
- Cellular interactions and factor generation were studied using conditioned media transfers and cell ghosts.
Main Results:
- DDG treatment of mixed peritoneal cells significantly enhanced macrophage ingestion activity.
- DDG treatment of macrophages alone did not enhance their activity, indicating a requirement for non-adherent cells.
- DDG-treated non-adherent cells generated a macrophage-activating signal factor, which involved B cells, T cells, and a serum factor.
Conclusions:
- Macrophage activation by DDG requires the cooperative action of non-adherent cells, specifically B and T lymphocytes.
- A rapid, cell-mediated signaling cascade involving a serum factor, B cells, and T cells leads to the generation of a potent macrophage-activating factor.
- The findings suggest a novel pathway for immune modulation involving alkylglycerols and cellular crosstalk.