Foscan® (mTHPC) photosensitized macrophage activation:: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-α-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 mu g ml(-1)) was studied in U937, monocyte cell line differentiated into macrophages (U937 Phi cells). Phagocytic activity of U937 Phi 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 1929 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(-1). 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.