Induction of systemic neutrophil response in mice by photodynamic therapy of solid tumors.
Photodynamic therapy (PDT) of solid tumors elicits a strong, acute inflammatory response characterized by a rapid and massive infiltration of activated neutrophils into the tumor. The present study investigated the impact of PDT on the systemic and local (treatment site) kinetics of neutrophil trafficking and activity in mouse SCCVII and EMT6 tumor models. Differential leukocyte counts in the peripheral blood of treated mice revealed a pronounced neutrophilia developing rapidly after Photofrin porfimer sodium (Photofrin)- or tetra(m-tetrahydroxyphenyl)chlorin (mTHPC)-based PDT. Significant neutrophilia was also observed upon PDT treatment of normal dorsal skin but not 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) expression was found among bone-marrow-residing neutrophils 6-24 h after PDT, and in neutrophils in the peripheral circulation and treated tumors 24 h after therapy. Complement inhibition completely prevented the development of PDT-induced neutrophilia. The results of the present study demonstrate that treatment of solid tumors by PDT induces a strong and protracted increase in systemic neutrophil numbers mediated by complement activation. This reaction reflects rapid and massive mobilization and activation of neutrophils for the destruction of PDT-treated tumor tissue.
Cecic
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Cancer Imaging Department, British Columbia Cancer Research Centre, 601 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
Parkins
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Korbelik
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy*; D003165:Complement System Proteins / Q000502:physiology; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use*; D007700:Kinetics; D019041:L-Selectin / Q000097:blood; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D013997:Time Factors
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D019041:L-Selectin; D003165:Complement System Proteins; D017323:Dihematoporphyrin Ether