title: Activation of macrophages by Photofrin II during photodynamic therapy.
abstract: In order to obtain information about the activation of macrophages (M phi s) during photodynamic therapy (PDT), the influence of Photofrin II (Pf II) on the viability of thioglycollate-elicited murine M phi s and the subsequent generation of superoxide anion was studied. Irradiations were performed at an energy density of 5 J cm-2, a power density of 150 mW cm-2 and a wavelength of 405 nm. Viability of M phi s 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 M phi s are highly susceptible to PDT as their viability is decreased to approximately 30% by 1 microgram ml-1 Pf II at the energy density indicated above. Within the first 30 min of addition of the photosensitizer, a reducing agent is generated intracellularly by the stimulation of the M phi s. An extracellular release of superoxide anion does not occur, as measured by the cyt c assay. Preincubation of the cells 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 phi s which could be interpreted as a first step for subsequent reactions.
authors.affiliation: Department of Surgery, Beckman Laser Institute and Medical Clinic, University of California, Irvine 92715.
authors.forename: R W
authors.initials: RW
authors.lastname: Steubing
authors.forename: S
authors.initials: S
authors.lastname: Yeturu
authors.forename: A
authors.initials: A
authors.lastname: Tuccillo
authors.forename: C H
authors.initials: CH
authors.lastname: Sun
authors.forename: M W
authors.initials: MW
authors.lastname: Berns
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism / Q000528:radiation effects; D017323:Dihematoporphyrin Ether; D005260:Female; D006415:Hematoporphyrins / Q000494:pharmacology*; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects* / Q000528:radiation effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009580:Nitroblue Tetrazolium; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D003574:Cytochrome c Group; D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D017323:Dihematoporphyrin Ether