Parasiticidal effect of δ-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells
Parasiticidal effect of δ-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells
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DOI：
10.1111/j.1600-0625.2007.00578.x
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发表时间：
2007-08-01
影响因子：
3.6
通讯作者：
Hasan, Tayyaba
中科院分区：
文献类型：
--
作者：
Akilov, Oleg E.;Kosaka, Sachiko;Hasan, Tayyaba
一些临床报告已经显示出用δ-氨基乙酰丙酸衍生的原卟啉IX（称为ALA-PDT）的光动力疗法作为皮肤利什曼病（CL）的治疗的有希望的但不是最佳的结果。因此，了解利什曼原虫对ALA-PDT的光毒性反应的基础可能是优化的关键。我们在这里报告在体外和体内的ALA-PDT对CL的机制研究。在与0.1 μ m ALA体外共孵育硕大利什曼原虫后，PpIX浓度保持在基础水平，而与0.1 μ m外源性PpIX共孵育后，PpIX水平高100倍。在利什曼原虫感染和未感染的J774.2细胞之间检测到ALA衍生的PpIX水平没有差异，并且PDT没有表现出对无鞭毛体的任何杀寄生虫作用。相比之下，在鼠CL模型上进行的体内局部ALA-PDT导致寄生虫负荷的显著减少和有力的组织破坏。ALA-PDT治疗后，感染皮肤中巨噬细胞的百分比显著降低，白细胞介素-6的水平升高。ALA-PDT观察到的临床结果可能是伴随巨噬细胞减少的非特异性组织破坏的结果，而不是直接杀死寄生虫。
Several clinical reports have shown promising, but not optimal, results from photodynamic therapy with delta-aminolevulinic acid-derived protoporphyrin IX, termed ALA-PDT, as a treatment for cutaneous leishmaniasis (CL). Therefore, understanding the basis of the phototoxic response of Leishmania parasites to ALA-PDT may be critical for optimization. We report here both in vitro and in vivo mechanistic studies of ALA-PDT against CL. Following in vitro co-incubation of Leishmania major with 0.1 mu m ALA, the PpIX concentration remained at the basal level, whereas after co-incubation with 0.1 mu m exogenous PpIX, the PpIX level was 100-fold higher. No differences in ALA-derived PpIX levels were detected between Leishmania-infected and non-infected J774.2 cells, and PDT did not demonstrate any parasiticidal effects on amastigotes. In contrast, in vivo topical ALA-PDT, performed on a murine CL model, resulted in significant reductions of the parasite loads and vigorous tissue destruction. After ALA-PDT, a dramatically decreased percentage of macrophages and increased levels of interleukin-6 were observed in the infected skin. The clinical outcome observed with ALA-PDT is likely the result of unspecific tissue destruction accompanied by depopulation of macrophages rather than direct killing of parasites.