Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acid
Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acid
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DOI：
10.1111/j.1346-8138.2007.00280.x
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发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Horio, Takeshi
中科院分区：
文献类型：
--
作者：
Hayami, Junji;Okamoto, Hiroyuki;Horio, Takeshi
光动力疗法(PDT)已被用于炎症性皮肤病以及浅表性皮肤癌，如日光角化症和鲍温病。采用小鼠接触性超敏反应(CHS)模型，研究局部应用氨基乙酰丙酸(ALA)和可见光照射的PDT是否具有与紫外线光疗相似的免疫抑制作用。PDT后1d，表皮朗格汉斯细胞(LC)数量减少，形态改变，5d达最低水平，以后逐渐恢复。相反，PDT后引流淋巴结CD11c(+)I-A(+)细胞数量显著增加。这表明LC从经PDT处理的皮肤中移出，导致表皮LC的减少并向淋巴结迁移。在20%ALA和40J/cm(2)可见光照射下，PDT处理的皮肤对DNFB的CHS反应明显抑制(局部免疫抑制)。当小鼠接受80J/cm(2)的PDT治疗时，CHS对施加在未经治疗的远处皮肤上的抗原的反应也显著受到抑制(全身免疫抑制)。对PDT局部或全身免疫抑制的小鼠，用DNFB对未处理的皮肤再次致敏，但诱发反应受到显著抑制。然而，这些小鼠能够被另一种半抗原--草松龙致敏。因此，局部应用ALA-PDT可诱导小鼠产生半抗原特异性免疫无反应(耐受)。这些发现表明，PDT对炎症性疾病的临床疗效具有潜在的免疫学贡献，与紫外线光疗相同。
Photodynamic therapy (PDT) has been used for inflammatory skin disorders as well as superficial skin cancers such as solar keratosis and Bowen's disease. Whether PDT with topical application of aminolevulinic acid (ALA) and exposure to visible light has a similar immunosuppressive action to ultraviolet phototherapy was investigated using a murine contact hypersensitivity (CHS) model. The number of epidermal Langerhans cells (LC) was decreased with their morphological changes 1 day after PDT with the minimal level at 5 days and gradual recovery thereafter. Conversely, the number of CD11c(+) I-A(+) cells was significantly increased in the draining lymph nodes after PDT. This suggests that LC moved from PDT-treated skin, resulting in the decrement of epidermal LC and migration to lymph nodes. CHS response to DNFB applied on the PDT-treated skin with 20% ALA and 40 J/cm(2) visible light was significantly suppressed (local immunosuppression). When mice were treated with 80 J/cm(2) of PDT, CHS response to the antigen applied on untreated distant skin was also significantly suppressed (systemic immunosuppression). The locally or systemically immunosuppressed mice by PDT were attempted to sensitize again with DNFB on non-treated skin, but elicitation responses were significantly suppressed. However, these mice were able to be sensitized with another hapten, oxasolone. Thus, a hapten-specific immunological unresponsiveness (tolerance) was induced in mice by topical ALA-PDT. These findings suggest that PDT has a potential immunological contribution to clinical efficacy for inflammatory diseases identical to ultraviolet phototherapies.