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Induction of Systemic Neutrophil Response in Mice by Photodynamic Therapy of Solid Tumors ¶
Author(s) -
Cecic Ivana,
Parkins Charles S.,
Korbelik Mladen
Publication year - 2001
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2001)0740712iosnri2.0.co2
Subject(s) - solid tumor , inflammatory response , photodynamic therapy , induction therapy , immunology , cancer research , medicine , chemistry , inflammation , cancer , chemotherapy , organic chemistry
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.