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Deletion of Alloantigen‐Activated Cells by Aminolevulinic Acid‐Based Photodynamic Therapy
Author(s) -
Hryhorenko Eric A.,
Oseroff Allan R.,
Morgan Janet,
RittenhouseDiakun Kate
Publication year - 1999
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 - 10.1111/j.1751-1097.1999.tb03327.x
Subject(s) - phototoxicity , photosensitizer , heme , photodynamic therapy , protoporphyrin ix , stimulation , mixed lymphocyte reaction , chemistry , in vitro , lymphocyte , intracellular , transplantation , protoporphyrin , cancer research , biochemistry , microbiology and biotechnology , immunology , biology , porphyrin , immune system , medicine , t cell , enzyme , endocrinology , photochemistry , organic chemistry
— Protoporphyrin IX (PpIX), an endogenously synthesized photosensitizer, can transiently accumulate in activated lymphocytes following administration of the heme precursor 5‐aminolevulinic acid (ALA). One possible mechanism of this in lymphocyte accumulation is that actively dividing cells use intracellular iron stores for cytochrome and DNA synthesis and thus do not inactivate PpIX, the photoactive precursor of heme, by iron incorporation. This selective accumulation in activated cells should allow targeting by photodynamic therapy (PDT). To determine the effect of this accumulation, we studied PDT effects on the in vitro correlate of transplantation rejection: the one‐way mixed lymphocyte reaction (MLR). Selective phototoxicity was determined by photoirradiating ALA‐treated, MLR‐activated cells and measuring subsequent stimulation either in a secondary MLR or with phytohemagglutinin (PHA). We found that proliferation of MLR‐activated lymphocytes incubated with ALA and treated with light was only 12–20% of controls (ALA+, no light) after rechallenge with the stimulator cells ( P < 0.05), although their response to nonspecific PHA stimulation was similar to controls. Thus alloantigen‐specific depletion was shown. The data suggest a role for ALAPDT in the treatment of diseases that require the selective elimination of activated lymphocytes and possibly as an immunomodulator.