PD-1 Regulates the Growth of Human Mastocytosis Cells
PD-1 Regulates the Growth of Human Mastocytosis Cells
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DOI：
10.2332/allergolint.12-oa-0450
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发表时间：
2013-03-01
影响因子：
6.8
通讯作者：
Haga, Hironori
中科院分区：
文献类型：
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作者：
Kataoka, Tatsuki R.;Fujimoto, Masakazu;Haga, Hironori
背景：程序性死亡-1 （PD-1）是人类肿瘤T细胞的标志物。在这里，我们评估了PD-1是否也是人肥大细胞增多症的标志物，并探讨了PD-1在人肥大细胞增多症细胞中的作用。方法：采用免疫组化方法检测PD-1在人皮肤肥大细胞增多症临床标本中的表达。采用RT-PCR、western blotting和流式细胞术检测PD-1在人肥大细胞增多症细胞株中的表达。用PD-1、PD-L1 （rPD-L1）重组配体刺激人肥大细胞增多症细胞系LAD2和HMC1.2，分别用细胞计数试剂盒-8和ELISA检测细胞增殖活性和信号分子状态。结果：30例皮肤肥大细胞增多症患者中有10例（33.3%）表达PD-1蛋白。我们还发现人类肥大细胞增生系LAD2细胞在其表面表达PD-1蛋白。rPD-L1抑制了LAD2细胞的干细胞因子依赖性生长。在LAD2细胞中，rPD-L1同时激活SHP-1和SHP-2，并降低AKT的磷酸化。相比之下，我们没有检测到PD-1的表达，也没有检测到rPD-L1对突变的kit驱动HMC1.2细胞生长的显著影响。结论：PD-1可作为人皮肤肥大细胞增多症的标志物，调节人皮肤PD-1阳性肥大细胞增多症细胞的生长。
Background: Programmed death-1 (PD-1) is a marker for human neoplastic T cells. Here, we evaluated whether or not PD-1 was also a marker for human mastocytosis, and explored the role of PD-1 in human mastocytosis cells.Methods: Immunohistochemical analysis was used to evaluate the expression of PD-1 in clinical samples of human cutaneous mastocytosis. The expression of PD-1 in human mastocytosis cell lines was checked by RT-PCR, western blotting and flow cytometry. We stimulated human mastocytosis cell lines (LAD2 and HMC1.2) with recombinant ligand for PD-1, PD-L1 (rPD-L1), and tested the proliferative activity and the status of signal molecules by Cell Counting Kit-8 and ELISA, respectively.Results: Ten of 30 human cutaneous mastocytosis cases (33.3%) expressed PD-1 protein. We also found that a human mastocytosis line LAD2 cells expressed PD-1 protein on their surfaces. The administration with rPD-L1 suppressed the stem cell factor-dependent growth of the LAD2 cells. And, rPD-L1 activated SHP-1 and SHP-2 simultaneously, and decreased the phosphorylation of AKT, in LAD2 cells. In contrast, we could not detect the expression of PD-1, and the significant effect of rPD-L1 on the mutated KIT-driven growth of HMC1.2 cells.Conclusions: PD-1 could be a marker for human cutaneous mastocytosis and regulate the growth of human PD-1-positive mastocytosis cells.