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Tumoricidal capacities of macrophages photodynamically activated with hematoporphyrin derivative
N Yamamoto1, J K Hoober, N Yamamoto
1Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140.
Abstract:
Four days after administration to mice of small amounts (30-600 ng/mouse) of hematoporphyrin derivative (HPD), peritoneal macrophages exhibited a greatly enhanced Fc-receptor mediated phagocytic capacity as assayed by ingestion activity of IgG-coated sheep erythrocytes. Much higher doses (greater than 3000 ng/mouse) did not have this effect. The peritoneal macrophages activated by administration of HPD have tumoricidal capacity for IgG-coated retinoblastoma cells. We then studied in vitro photodynamic activation of macrophages by white and red fluorescent light irradiation of mouse peritoneal cells (mixture of macrophages and B and T lymphocytes) in media containing very low concentrations of HPD. A short (5 s) white fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.03 ng HPD/mL produced the maximal level of ingestion activity of macrophages. A 15 s red fluorescent light exposure (1Wm-2) of peritoneal cells in a medium containing 0.1 ng HPD/mL produced the maximal level of ingestion activity of macrophages. Thus, photodynamic activation of macrophages with white fluorescent light is more efficient than that with red fluorescent light. This can be explained by the fact that HPD has a large absorption peak at about 364 nm which extends into the visible range, and decreasingly smaller absorption bands at 500, 535, 570 and 630 nm. In vitro photodynamically activated macrophages showed efficient tumoricidal activity regardless of the type (white or red) of light used. These results suggest that a low level of HPD promotes therapeutic immunopotentiation.
Insights
Low doses of hematoporphyrin derivative (HPD) enhance macrophage immune activity and tumoricidal capacity. Photodynamic activation in vitro with white light proved more efficient than red light for boosting these therapeutic immune responses.
Area of Science:
- Immunology
- Photodynamic Therapy
- Cell Biology
Background:
- Hematoporphyrin derivative (HPD) is a photosensitizer used in photodynamic therapy.
- Macrophages play a crucial role in the immune response and tumor surveillance.
- Understanding how HPD affects macrophage function is important for developing novel immunotherapies.
Purpose of the Study:
- To investigate the effect of hematoporphyrin derivative (HPD) on the phagocytic and tumoricidal capacity of mouse peritoneal macrophages.
- To evaluate the efficacy of in vitro photodynamic activation of macrophages using different light sources and concentrations of HPD.
Main Methods:
- Administration of varying doses of HPD to mice and subsequent assay of peritoneal macrophage phagocytic activity.
- In vitro photodynamic activation of mouse peritoneal cells (macrophages, B and T lymphocytes) using white and red fluorescent light in the presence of HPD.
- Assay of macrophage ingestion activity and tumoricidal capacity against IgG-coated sheep erythrocytes and retinoblastoma cells, respectively.
Main Results:
- Low doses of HPD (30-600 ng/mouse) significantly enhanced Fc-receptor mediated phagocytic capacity of peritoneal macrophages.
- Higher doses of HPD (>3000 ng/mouse) did not elicit this enhancement.
- In vitro, photodynamic activation with white fluorescent light (5s, 1Wm-2, 0.03 ng HPD/mL) was more efficient in maximizing macrophage ingestion activity than red light (15s, 1Wm-2, 0.1 ng HPD/mL).
- Photodynamically activated macrophages exhibited efficient tumoricidal activity against retinoblastoma cells.
Conclusions:
- Low-level HPD administration can potentiate the immune system, specifically enhancing macrophage function.
- Photodynamic activation of macrophages is a viable strategy for immunotherapy.
- White fluorescent light is more efficient than red light for in vitro photodynamic activation of macrophages, likely due to HPD's absorption spectrum.