Induction of systemic neutrophil response in mice by photodynamic therapy of solid tumors

Photodynamic therapy (PDT) of solid tumors elicits a strong, acute inflamma tory response characterized by a rapid and massive infiltration of activate d neutrophils into the tumor. The present study investigated the impact of PDT on the systemic and local (treatment site) kinetics of neutrophil traff icking and activity in mouse SCCVII and EMT6 tumor models. Differential leu kocyte counts in the peripheral blood of treated mice revealed a pronounced neutrophilia developing rapidly after Photofrin porfimer sodium (Photofrin )- or tetra(m-tetrahydroxy-phenyl)chlorin (mTHPC)-based PDT. Significant ne utrophilia was also observed upon PDT treatment of normal dorsal skin but n ot on the footpad of tumor-free mice. The changes in circulating neutrophil numbers were accompanied by an efflux of these cells from the bone marrow. An increased proportion of cells with high L-selectin (CD62L antigen) expr ession was found among bone-marrow-residing neutrophils 6-24 h after PDT, a nd in neutrophils in the peripheral circulation and treated tumors 24 h aft er therapy. Complement inhibition completely prevented the development of P DT-induced neutrophilia. The results of the present study demonstrate that treatment of solid tumors by PDT induces a strong and protracted increase i n systemic neutrophil numbers mediated by complement activation. This react ion reflects rapid and massive mobilization and activation of neutrophils f or the destruction of PDT-treated tumor tissue.