Foscan (mTHPC) photosensitized macrophage activation: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-alpha-mediated cytolytic activity.
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.
Coutier
S
S
Unité de Recherche en Thérapie Photodynamique, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France.
Bezdetnaya
L
L
Marchal
S
S
Melnikova
V
V
Belitchenko
I
I
Merlin
J L
JL
Guillemin
F
F
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007739:L Cells; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008652:Mesoporphyrins / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology; D020298:U937 Cells
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C072269:temoporfin