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SENSITIVITY OF ACTIVATED MURINE PERITONEAL MACROPHAGES TO PHOTODYNAMIC KILLING WITH BENZOPORPHYRIN DERIVATIVE
- Source :
- Photochemistry and Photobiology. 61:417-421
- Publication Year :
- 1995
- Publisher :
- Wiley, 1995.
-
Abstract
- — This study compared the ability of highly purified resting and activated DBA/2 mouse peritoneal macrophages to survive treatment with the photosensitizer benzoporphyrin derivative (BPD, verteporfin) and light. Culture of macrophages with recombinant murine interferon-γ (rIFN-γ, 100 U/mL) for 72 h imparted a phenotypic and functional activation by dramatically increasing cell surface expression of major histocompatibility complex Class II (Ia) molecules and the formation of nitric oxide. The rIFN-γ-activated macrophages were significantly (P < 0.05) more sensitive (lethal dose to cause a 50% reduction in cell survival, LD50= 14.4 ± 1.1 ng/mL) to photodynamic killing with BPD and light (10 J/cm2) than cells (LD50= 18.2 ± 2.0 ng/mL) cultured in medium alone. In contrast, macrophages treated with different concentrations of bacterial lipopolysaccharide (LPS) were as resistant or more resistant to photodynamic killing than cells cultured in medium alone. No cytotoxic effect of BPD was detected in cultures containing the drug but protected from light. Comparable amounts of BPD were taken up in vitro by unactivated and rIFN-γ-activated macrophages, as detected by flow cytometric analysis. However, cells cultured with LPS (10 μg/mL) took up more BPD than macrophages cultured in medium alone or with rIFN-γ. The DBA/2 P815 mastocytoma cells took up greater amounts of the drug and were subsequently more vulnerable to treatment with BPD and light (LD50= 6.9 ng/mL) than macrophages cultured under any condition. The explanation for the increased vulnerability of rIFN-γ-activated macrophages and the greater resistance of LPS-activated macrophages, relative to medium-cultured macrophages, to photodynamic killing with BPD is uncertain. However, the increased susceptibility of macrophages, activated with the immunomodulatory cytokine IFN-γ, to treatment with BPD and light might indicate how photodynamic therapy could interfere with the development of experimental autoimmune disease, conditions in which activated macrophages are known to be involved.
- Subjects :
- Cytotoxicity, Immunologic
Male
Porphyrins
Lipopolysaccharide
medicine.medical_treatment
Photodynamic therapy
In Vitro Techniques
Biochemistry
Mice
chemistry.chemical_compound
Interferon
Tumor Cells, Cultured
medicine
Animals
Cytotoxic T cell
Physical and Theoretical Chemistry
Photosensitizing Agents
Lethal dose
Verteporfin
General Medicine
Macrophage Activation
Molecular biology
In vitro
Cytokine
Photochemotherapy
chemistry
Mice, Inbred DBA
Immunology
Macrophages, Peritoneal
medicine.drug
Subjects
Details
- ISSN :
- 17511097 and 00318655
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Photochemistry and Photobiology
- Accession number :
- edsair.doi.dedup.....361c76cc00122d4e94d335fbbe2a2a9b