Foscan (mTHPC) photosensitized macrophage activation: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-alpha-mediated cytolytic activity.
Fiche publication
Date publication
septembre 1999
Journal
British journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MERLIN Jean-Louis
Tous les auteurs :
Coutier S, Bezdetnaya L, Marchal S, Melnikova V, Belitchenko I, Merlin JL, Guillemin F
Lien Pubmed
Résumé
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 microg ml(-1)) was studied in U937, monocyte cell line differentiated into macrophages (U937) cells). Phagocytic activity of U937phi 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-alpha) by photosensitized macrophages was further demonstrated using the L929 assay. The maximum TNF-alpha 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.
Mots clés
Animals, Cell Differentiation, drug effects, Cytotoxicity, Immunologic, drug effects, Humans, L Cells (Cell Line), Macrophage Activation, drug effects, Macrophages, drug effects, Mesoporphyrins, pharmacology, Mice, Nitric Oxide, metabolism, Phagocytosis, drug effects, Photochemotherapy, Photosensitizing Agents, pharmacology, Tumor Necrosis Factor-alpha, biosynthesis, U937 Cells
Référence
Br. J. Cancer. 1999 Sep;81(1):37-42