EFFECTS OF PHOTODYNAMIC TREATMENT OF PLATELETS OR ENDOTHELIAL CELLS in vitro ON PLATELET AGGREGATION

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Abstract
—: The purpose of this work was to gain insight into the role played by platelets and endothelial cells in the development of thrombogenic vascular events, observed after in vivo photodynamic therapy (PDT), by studying the in vitro effects of PDT on isolated human platelets and cultured human and bovine endothelial cells. Exposure to Photofrin II (PII) and light caused platelets to rapidly lose their ability to aggregate. Photofrin II alone at high concentrations also exerted inhibitory effects on aggregation. Endothelial cells exposed to PII‐ and phthalocyanine (GaCI‐PcS2,3 or Zn‐PCS1,2)‐mediated PDT released potent platelet anti‐ and disaggregating activity which could be identified as prostacyclin by the following criteria: a close correlation between the time and dose dependent anti‐aggregating effects and released 6‐keto‐PGF1α (the spontaneous hydrolysis praduct of PGI, determined by radioimmunoassay), the inhibition of these effects by indomethacin, accumulation of 6‐keto‐PGF1α metabolite in the media of cells treated with PDT (as determined by HPLC analysis), and the absence of evidence for significant nitric oxide production. This prostacyclin release occurred following plasma membrane damage. Although no pro‐aggregating activity was observed, endothelial cells were found to release considerable amounts of arachidonic acid and prostaglandin F2α in response to PDT. These data, which indicate powerful anti‐thrombogenic effects in vitro, are in sharp contrast to the vascular effects of PDT in vivo which are characterized by severe platelet aggregation, and imply that the in vivo effects involve additional components of the vascular system.