Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes.

Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes.
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发表时间:
1991-06
期刊:
影响因子:
11.2
通讯作者:
T. Utsugi;A. Schroit;J. Connor;C. Bucana;I. Fidler
T. Utsugi;A. Schroit;J. Connor;C. Bucana;I. Fidler
中科院分区:
医学1区
文献类型:
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作者:
T. Utsugi;A. Schroit;J. Connor;C. Bucana;I. Fidler

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我们确定是否存在磷脂酰丝氨酸(PS)在人类肿瘤细胞的外膜小叶与他们的识别激活的人单核细胞。三种致瘤细胞系,A375黑色素瘤和A431和科洛-16癌,以及正常人表皮角质形成细胞系(NHEK)与单核细胞一起孵育,单核细胞通过γ-干扰素和脂多糖活化至杀肿瘤状态。活化的人单核细胞结合并裂解所有致瘤靶点,而非致瘤NHEK既不结合也不杀死。半定量分析的PS外叶的细胞显示,致瘤细胞表达的PS比非致瘤NHEK的3 - 7倍。为了确定肿瘤细胞上增强的PS表达是否是它们被活化的单核细胞识别的原因,向NHEK补充外源性提供的PS和磷脂酰胆碱的类似物。PS标记的NHEK与活化的人单核细胞结合,但磷脂酰胆碱标记的NHEK和对照NHEK均未结合。这些结果表明PS在单核细胞识别肿瘤细胞中的作用。
We determined whether the presence of phosphatidylserine (PS) in the outer membrane leaflet of human tumor cells correlated with their recognition by activated human monocytes. Three tumorigenic cell lines, A375 melanoma and A431 and Colo-16 carcinomas, and a normal human epidermal keratinocyte line (NHEK) were incubated with monocytes activated to the tumoricidal state by gamma-interferon and lipopolysaccharide. Activated human monocytes bound to and lysed all tumorigenic targets, while the nontumorigenic NHEK were neither bound nor killed. Semiquantitative analysis of PS in the outer leaflet of the cells revealed that the tumorigenic cells expressed 3-7-fold more PS than did the nontumorigenic NHEK. To determine whether enhanced PS expression on the tumor cells was responsible for their recognition by activated monocytes, NHEK were supplemented with exogenously supplied analogues of PS and phosphatidylcholine. PS-labeled NHEK but not phosphatidylcholine-labeled nor control NHEK bound to activated human monocytes. These results suggest a role for PS in monocyte recognition of tumor cells.