Activation of macrophages by Photofrin II during photodynamic therapy

Abstract

In order to obtain information about the activation of macrophages (M&s) during photodynamic therapy (PDT), the influence of Photofrin II (Pf II) on the viability of thioglycollate-elicited murine M4.s and the subsequent generation of superoxide anion was studied. Irradiations were performed at an energy density of 5 J cme2, a power density of 150 mW cmm2 and a wavelength of 405 run. Viability of M& was assessed using the acridine orange-ethidium bromide assay. Superoxide anion generation was determined using ferricytochrome c (cyt c) and nitroblue tetrazolium (NBT) reduction. Our results indicate that the MC@ are highly susceptible to PDT as their viability is decreased to approximately 30% by 1 pg ml-' Pf II at the energy density indicated above. Within the tirst 30 min of addition of the photosensitizer, a reducing agent is generated intracellularly by the stimulation of the M&s. An extracellular release of superoxide anion does not occur, as measured by the cyt c assay. Preincubation of the ceils for 1 or 24 h with Pf II and a second challenge with phorbol myristate acetate (PMA) does not enhance the reduction of NBT. Thus, Pf II exerts an immediate effect on the M+s which could be interpreted as a first step for subsequent reactions.

Amplification of cancer cell apoptosis in photodynamic therapy-treated tumors by adjuvant ceramide analog LCL29

“…The former contain resident well‐differentiated macrophages highly specialized in phagocytic activity that evidently show high phalloidin staining. However, these cells are extremely efficient in accumulating high levels of photosensitizing drugs 40, which makes them particularly vulnerable to lethal effects of PDT 39. Thus, at 3 hours after PDT treatment (chosen in the present study) the old resident macrophages are largely destroyed and replaced by newly‐infiltrated monocytes/macrophages characterized by low phalloidin staining.…”

“…A major role of professional phagocytes is to remove these dying cells in order to prevent deleterious effects such as protracted inflammation and the development of autoimmune reaction. Since macrophages found in PDT treated tumors are known to become activated and engaged in engulfment of dying cells and their debris 23, 25, 39, total counts of apoptotic cells in these tumors are always underestimated as exact numbers cannot be determined due to their constant removal. We assessed instead the level of phagocytic activity in macrophages from PDT‐treated tumors by phalloidin‐based staining for F‐actin 21.…”

Stimulation of anti-tumor immunity by photodynamic therapy

“…Macrophages can be activated by low sublethal doses of PDT [53] and secrete TNF-α [54] by a PDT-related increase in macrophage -activating factor [55,56]. Evidence also indicates that macrophages can show preferential cytotoxicity towards tumor cells treated with a sub-lethal dose of PDT [57] and that this effect may be due to potential interaction between macrophages and natural killer cells (NK) [58].…”

Photodynamic therapy induces an immune response against a bacterial pathogen

“…Additionally, macrophages secrete cytokines, chemokines and other mediators essential in the development of PDT-mediated inflammation. Macrophages can be activated by low PDT doses (non-lethal) and secrete TNF-α [30,31]. The presence of HSP70 secreted by apoptotic and necrotic cells seems to be essential for macrophage activation [32].…”