A functional study on the migration of human monocytes to human leukemic cell lines and the role of monocyte chemoattractant protein-1

A functional study on the migration of human monocytes to human leukemic cell lines and the role of monocyte chemoattractant protein-1
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DOI:
10.1038/sj.leu.2400848
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发表时间:
1997-11-01
期刊:
影响因子:
11.4
通讯作者:
Ossenkoppele, GJ
Ossenkoppele, GJ
中科院分区:
医学1区
文献类型:
--
作者:
Legdeur, MCJC;Beelen, RHJ;Ossenkoppele, GJ

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在本研究中,人单核细胞向五种不同的人髓性白血病细胞系,四种不同的人淋巴细胞白血病细胞系和来自三种不同的急性髓性白血病(AML)患者的原始细胞的上清液的迁移进行了研究,单核细胞趋化蛋白(MCP)-1的作用建立与ELISA测定。单核细胞向白血病细胞上清液迁移的差异较大(与阳性对照相比,变化约为10 - 150%),但大量单核细胞迁移始终限于髓系白血病细胞(细胞系或患者原始细胞)。MCP-1在迁移中起主要作用,首先是因为迁移量与上清液中MCP-1的浓度之间存在直接相关性,其次是因为在所有情况下添加抗hMCP-1能够抑制迁移至背景水平。使用MCP-1刺激的单核细胞对两种人髓性白血病细胞系进行MTT试验的细胞毒性实验显示,与未刺激的单核细胞相比,细胞死亡没有增加。它的结论是,单核细胞向白血病细胞的迁移被限制在髓系和MCP-1,这是由白血病细胞产生的不同数量的调节。此外,MCP-1不增加单核细胞对白血病细胞的直接毒性作用。
In the present study the migration of human monocytes towards the supernatants of five different human myeloid leukemic cell lines, four different human lymphatic leukemic cell lines and blasts derived from three different patients with acute myeloid leukemia (AML) was studied and the role of monocyte chemoattractant protein (MCP)-1 was established with an ELISA assay. Large differences in migration of monocytes towards the leukemic cell supernatants were shown (variation of approximately 10 to 150% compared to positive control), but high amounts of monocyte migration was always restricted to myeloid leukemic cells (cell lines or patient blasts). MCP-1 turned out to play a major role in the migration, firstly since there was a direct correlation between the amount of migration and the concentration of MCP-1 in the supernatants, and secondly since the addition of anti-hMCP-1 was able to inhibit migration to background level in all cases. Cytotoxicity experiments with a MTT test using MCP-1-stimulated monocytes against two human myeloid leukemic cell lines showed no increase in cell death compared to unstimulated monocytes. It is concluded that monocyte migration towards leukemic cells is restricted to the myeloid lineage and is regulated by MCP-1, which is produced in different amounts by the leukemic cells. Besides, MCP-1 does not increase the direct toxic effects of monocytes on leukemic cells.