Foscan® (mTHPC) photosensitized macrophage activation: Enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-α-mediated cytolytic activity

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Abstract

Photodynamic activation of macrophage-like cells contributes to an effective outcome of photodynamic therapy (PDT) treatment. The possibility for an enhancement of macrophage activity by photosensitization with meta-tetra(hydroxyphenyl)chlorin (mTHPC) (1 μg ml-1) was studied in U937, monocyte cell line differentiated into macrophages (U937Φ cells). Phagocytic activity of U937Φ cells was evaluated by flow-cytometry monitoring of ingestion of fluorescein-labelled Escherichia coli particles. Increase in irradiation fluence up to 3.45 mJ cm-2 (corresponding irradiation time 15 s) resulted in significant increase in fluorescence signal (145%), while at higher light fluences the signal lowered down to the untreated control values. A light energy-dependent production of tumour necrosis factor-alpha (TNF-α) by photosensitized macrophages was further demonstrated using the L929 assay. The maximum TNF-α mediated cytolysis was observed at 28 mJ cm-2 and was 1.7-fold greater than that in control. In addition, we demonstrated a fluence-dependent increase in nitric oxide (NO) production by mTHPC-photosensitized macrophages. NO release increased gradually and reached a plateau after irradiation fluence of 6.9 mJ cm-2. Cytotoxicity measurements indicated that the observed manifestations of mTHPC-photosensitized macrophage activation took place under the sublethal light doses. The relevance of the present findings to clinical mTHPC-PDT is discussed.

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Coutier, S., Bezdetnaya, L., Marchal, S., Melnikova, V., Belitchenko, I., Merlin, J. L., & Guillemin, F. (1999). Foscan® (mTHPC) photosensitized macrophage activation: Enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-α-mediated cytolytic activity. British Journal of Cancer, 81(1), 37–42. https://doi.org/10.1038/sj.bjc.6690648

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