Effectiveness of photofrin II in activation of macrophages and in vitro killing of retinoblastoma cells.
Administration of a small dose (300 ng/mouse) of photofrin II (PII) to mice, followed by 4 days of exposure to only ambient fluorescent light in animal quarters, induced Fc-receptor-mediated phagocytic and superoxide-generating capacities of peritoneal macrophages by five- and seven-fold, respectively. When these mice were kept in the dark for 4 days, no activation of macrophages was observed. These results suggest that macrophage activation is a consequence of photodynamic activation. Much higher doses (> 3000 ng/mouse) suppressed macrophage activity. However, 2 months after administration of 3000 ng PII/mouse, greatly enhanced phagocytic and superoxide-generating capacities of peritoneal macrophages were observed. In vitro photodynamic activation of macrophages was analyzed after white or red fluorescent light exposure of mouse peritoneal cells (mixture of macrophages and B and T lymphocytes) in media containing PII. A short (10 s) white fluorescent light treatment of peritoneal cells in a medium containing 0.03 ng PII/mL produced the maximal level of phagocytic activity of macrophages. Illumination with the same total fluence of red fluorescent light requires a three-fold higher concentration of PII to achieve the same extent of enhanced phagocytic activity of macrophages. Thus, photodynamic activation of macrophages with PII by white fluorescent light was more efficient than by red fluorescent light. Similarly, photodynamic killing of retinoblastoma cells was more efficient with white than red fluorescent light. The concentration of hematoporphyrin (HP) or PII required for direct photodynamic killing of retinoblastoma cells was roughly four orders of magnitude greater than that required for activation of macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamamoto
N
N
Albert Einstein Cancer Center, Philadelphia, PA 19141.
Sery
T W
TW
Hoober
J K
JK
Willett
N P
NP
Lindsay
D D
DD
D000818:Animals; D017323:Dihematoporphyrin Ether / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D012175:Retinoblastoma / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D017323:Dihematoporphyrin Ether