Chemokine system and tissue infiltration in aggressive NK-cell leukemia
Chemokine system and tissue infiltration in aggressive NK-cell leukemia
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DOI：
10.1016/j.leukres.2006.10.020
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发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Ishida, Fumihiro
中科院分区：
文献类型：
--
作者：
Makishima, Hideki;Ito, Toshiro;Ishida, Fumihiro
NK细胞型颗粒淋巴细胞淋巴增殖性疾病可细分为侵袭性NK细胞白血病（ANKL）和慢性NK细胞淋巴细胞增多症（CNKL）。 ANKL 患者可观察到肝脾肿大，肝衰竭是常见的死亡原因。在肝窦和小叶间区域以及脾红髓中病理学观察到大量 ANKL 细胞。在我们之前的研究中，ANKL细胞CXCR1和CCR5同时呈阳性。因此，为了阐明ANKL细胞全身迁移的机制，我们比较了ANKL和CNKL中相应趋化因子的表达。 ANKL患者血清IL-8、MIP-1α和MIP-1β水平显着升高，细胞内染色和RT-PCR显示ANKL细胞IL-8、RANTES、MIP-1α和MIP-1β高度阳性。这些趋化因子在肝细胞中也呈阳性染色。 Fas 和 Fas 配体 (FasL) 之间的相互作用被认为是 ANKL 肝功能障碍的机制之一。 ANKL患者血清中可溶性FasL浓度显着升高，ANKL细胞胞质中表达FasL蛋白。这些结果表明趋化因子系统在表达FasL的ANKL细胞的迁移中发挥重要作用。 (c) 2006 Elsevier Ltd. 保留所有权利。
NK cell-type lymphoproliferative disease of granular lymphocytes can be subdivided into aggressive NK-cell leukemia (ANKL) and chronic NK-cell lymphocytosis (CNKL). Hepatosplenomegaly is observed in ANKL patients, and hepatic failure is a common cause of death. Significant numbers of ANKL cells were pathologically observed in sinusoidal and interlobular regions of the liver, and in the splenic red pulp. In our previous study, ANKL cells were simultaneously positive for CXCR1 and CCR5. So, in order to elucidate the mechanism in the systemic migration of ANKL cells, we investigated the expression of the corresponding chemokines in ANKL compared with CNKL. The serum level of IL-8, MIP-1 alpha and MIP-1 beta was significantly elevated in ANKL patients, and ANKL cells were highly positive for IL-8, RANTES, MIP-1 alpha and MIP-1 beta according to intracellular staining and RT-PCR. These chemokines were also positively stained in heparocytes. The interaction between Fas and Fas ligand (FasL) is supposed to be one of the mechanisms for liver dysfunction in ANKL. The serum concentration of soluble FasL was significantly high in ANKL patients, and ANKL cells expressed FasL protein in the cytoplasm. These results suggest that the chemokine system plays an important role in the transmigration of FasL-expressing ANKL cells. (c) 2006 Elsevier Ltd. All rights reserved.