Cecic Ivana, Sun Jinghai, Korbelik Mladen
British Columbia Cancer Agency, Vancouver, BC, Canada.
Photochem Photobiol. 2006 Mar-Apr;82(2):558-62. doi: 10.1562/2005-09-09-RA-681.
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.
光动力疗法（PDT）治疗肿瘤会引发宿主保护性炎症和急性期反应以及免疫反应。在这种情况下出现的中性粒细胞增多是由活化补体系统精心协调的多种中性粒细胞趋化介质驱动的。本研究使用小鼠FsaR纤维肉瘤进一步研究基于卟吩姆钠的光动力疗法诱导的中性粒细胞增多。补体过敏毒素C3a被确定为光动力疗法诱导的中性粒细胞增多晚期的主要趋化因子，因为给小鼠注射阻断其受体C3aR的抗体可显著抑制光动力疗法后8小时中性粒细胞水平的升高。在同一时间点，在宿主小鼠血液中的中性粒细胞、单核细胞和B淋巴细胞中检测到C3aR表达增加。从未接受过治疗的小鼠中收集的腹膜巨噬细胞和肥大细胞在体外与经光动力疗法处理的FsaR细胞共孵育8小时后，C3aR表达升高。因此，C3a成为参与光动力疗法诱导的宿主反应的关键效应分子之一。
