Inhibitory effects of merocyanine 540-mediated photodynamic therapy on cellular immune functions: A role in the prophylaxis of graft-versus-host disease?

Inhibitory effects of merocyanine 540-mediated photodynamic therapy on cellular immune functions: A role in the prophylaxis of graft-versus-host disease?
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DOI:
10.1016/j.jphotobiol.2015.09.012
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发表时间:
2015-12
期刊:
Journal of photochemistry and photobiology. B, Biology
影响因子:
--
通讯作者:
Sieber F
Sieber F
中科院分区:
其他
文献类型:
--
作者:
Traul DL;Sieber F

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Mercury 540介导的光动力疗法(MC 540-PDT)已用于临床试验,用于净化自体造血干细胞移植物。当将相同的染料和光的组合应用于人外周血淋巴细胞时,广泛的T细胞和B细胞功能受损,促使人们猜测MC 540-PDT在预防移植物抗宿主病(GVHD)中的潜在作用。本文报道了MC 540-PDT对小鼠淋巴细胞体外功能的影响,并初步评价了MC 540-PDT对小鼠异基因骨髓移植模型GVHD的预防作用。中等剂量的MC 540-PDT可抑制混合淋巴细胞反应、凝集素、白细胞介素-2和脂多糖的增殖反应、T细胞介导的溶解和NK活性。MC 540-PDT是否降低异基因造血干细胞移植小鼠模型中GVHD的发生率和/或严重程度取决于错配移植物的组成和制备方案的强度。MC 540-PDT仅在移植物的脾细胞含量低和/或准备方案的辐射剂量不是清髓性的时是有益的(即降低GVHD的发生率和/或严重性),并且因此可能促进混合嵌合体。
Merocyanine 540-mediated photodynamic therapy (MC540-PDT) has been used in clinical trials for the purging of autologous hematopoietic stem cells grafts. When the same combinations of dye and light were applied to human peripheral blood lymphocytes, a broad range of T- and B-cell functions were impaired, prompting speculations about a potential role of MC540-PDT in the prophylaxis of graft-versus-host disease (GVHD). We here report on the effects of MC540-PDT on in vitro functions of murine lymphocytes as well as a preliminary evaluation of MC540-PDT for the prevention of GVHD in murine models of allogeneic bone marrow transplantation. Mixed lymphocyte reactions, proliferative responses to lectins, interleukin-2 and lipopolysaccharide, T-cell-mediated lysis, and NK activity were all inhibited by moderate doses of MC540-PDT. Whether MC540-PDT reduced the incidence and/or the severity of GVHD in murine models of allogeneic hematopoietic stem cell transplantation depended on the composition of the mismatched grafts and the intensity of the preparative regimen. MC540-PDT was only beneficial (i.e. reduced the incidence and/or severity of GVHD) when the spleen cell content of grafts was low and/or the radiation dose of the preparative regimen was not myeloablative, and, therefore, may have encouraged mixed chimerism.