Erythrocytes - the house elves of photodynamic therapy

Photodynamic therapy (PDT) and fluorescence diagnosis (FD) are being developed for a number of clinical applications. Since fluorophores and photosensitising drugs are usually given systemically their effect on blood elements are of significant importance. Photodynamic effects on erythrocytes occur naturally in patients with erythropoietic protoporphyria (EPP). Exposure to small fluences, as obtained by the erythrocytes when they pass capillaries in the skin, leads to transfer of the photosensitiser protoporphyrin IX (PP IX), from EPP erythrocytes to endothelial cells. Thus, the erythrocytes are partly protected while the endothelial cells suffer photo-damage. During photodynamic therapy in vivo erythrocytes are regularly photosensitised. This side effect is partly intended but mostly unwanted, and a summary of this topic is given. Furthermore, the effect of UV-A on erythrocytes that is accompanied with the formation of bilirubin is reviewed. Erythrocytes serve as convenient model cells for experimental research. Such use of erythrocytes to screen new photosensitisers may be of limited value. A combination of photohaemolysis and haemoglobin oxygenation may become the basis for an assay for in vitro phototoxicity. Erythrocytes from birds are good model cells for exploration of physiological and molecular mechanisms involved in PDT. A potential mechanism of PDT induced behaviour resembling apoptosis in erythrocytes is provided. PDT for sterilisation of erythrocyte concentrates has a potential for medical use. Photodynamic effects on the erythrocytes themselves should be avoided. This is realised by choosing a virus-selective photosensitiser, low fluences and treatment of the concentrates with agents like dipyridamole and antioxidants. Future aspects of applications of photosensitisation of red blood cells are discussed.