Role of complement anaphylatoxin C3a in photodynamic therapy-elicited engagement of host neutrophils and other immune cells.
Tumor treatment by photodynamic therapy (PDT) provokes a host-protective inflammatory and acute-phase response and an immune reaction. Neutrophilia manifested in this context is driven by multiple mediators of neutrophil chemotaxis orchestrated by an activated complement system. Mouse FsaR fibrosarcoma was used in this study to further investigate neutrophilia induced by Photofrin-based PDT. The complement anaphylatoxin C3a was identified as a major chemoattractant in the advanced phase of PDT-induced neutrophilia, because injecting mice with antibodies blocking its receptor C3aR significantly inhibited the increase in neutrophil levels 8 h after PDT. At the same time point, an increased C3aR expression was detected in neutrophils, monocytes and B lymphocytes in the blood of host mice. Peritoneal macrophages and mast cells harvested from treatment-naive mice exhibited elevated C3aR expression after coincubation in vitro for 8 h with PDT-treated FsaR cells. Thus, C3a emerges as one of the key effector molecules engaged in PDT-induced host response.
Cecic
Ivana
I
British Columbia Cancer Agency, Vancouver, BC, Canada.
Sun
Jinghai
J
Korbelik
Mladen
M
D000706:Anaphylatoxins / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D015926:Complement C3a / Q000276:immunology*; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D010778:Photochemotherapy; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000706:Anaphylatoxins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015926:Complement C3a