Tai G, Eun-Young J, Yuji H, Masahiko K, Toshio H, Kenji K, Kenshi F, Mitsufumi M
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Hematol Oncol. 1996 Dec;14(4):181-92. doi: 10.1002/(SICI)1099-1069(199612)14:4<181::AID-HON589>3.0.CO;2-Y.
A human eosinophilic leukemia cell line, EoL-1, stopped proliferating at the G1 phase, differentiated into eosinophilic granule-containing cells, and died by apoptosis when stimulated with dibutyryl cyclic AMP (dbcAMP). To clarify the effects of dbcAMP, the effects of butyrate and cAMP-increasing reagents, prostaglandin E2 (PGE2) and forskolin, on EoL-1 cellular differentiation and apoptosis were examined and compared. PGE2 and forskolin but not butyrate induced differentiation to eosinophilic granule-containing cells, suggesting that cAMP played a primary role in eosinophilic differentiation of EoL-1 cells. PGE2, forskolin and butyrate, when used alone, did not induce apoptosis of EoL-1 cells significantly at the concentrations used, but sequential stimulation of EoL-1 cells with the cAMP-increasing reagents and butyrate showed that butyrate induced further maturation and apoptosis of cAMP-induced eosinophilic granule-containing cells. These results showed that cAMP and butyrate have different effects on eosinophilic differentiation and apoptosis of EoL-1 cells. The cAMP-increasing reagents and butyrate also showed different effects on expression of members of the bcl-2 family; PGE2 decreased bcl-2 and bax levels, whereas butyrate increased the bcl-2 level. PGE2 or PGE2+butyrate, but not butyrate alone, induced bcl-XS expression. EoL-1 cells constitutively expressed Fas and anti-Fas antibody induced EoL-1 cell death, but the Fas/Fas ligand system was not involved in dbcAMP-induced EoL-1 cell apoptosis. The EoL-1 cell line is thus a useful model in which to examine differentiation and apoptosis of eosinophilic leukemia cells.
一种人类嗜酸性粒细胞白血病细胞系EoL-1，在G1期停止增殖，分化为含嗜酸性颗粒的细胞，并在受到二丁酰环磷腺苷（dbcAMP）刺激时通过凋亡死亡。为了阐明dbcAMP的作用，研究并比较了丁酸盐和增加cAMP的试剂前列腺素E2（PGE2）及福斯高林对EoL-1细胞分化和凋亡的影响。PGE2和福斯高林而非丁酸盐诱导细胞分化为含嗜酸性颗粒的细胞，这表明cAMP在EoL-1细胞的嗜酸性分化中起主要作用。PGE2、福斯高林和丁酸盐单独使用时，在所使用的浓度下均未显著诱导EoL-1细胞凋亡，但用增加cAMP的试剂和丁酸盐对EoL-1细胞进行顺序刺激显示，丁酸盐可诱导cAMP诱导的含嗜酸性颗粒的细胞进一步成熟和凋亡。这些结果表明，cAMP和丁酸盐对EoL-1细胞的嗜酸性分化和凋亡有不同影响。增加cAMP的试剂和丁酸盐对bcl-2家族成员的表达也有不同影响；PGE2降低了bcl-2和bax水平，而丁酸盐则提高了bcl-2水平。PGE2或PGE2+丁酸盐而非单独的丁酸盐诱导了bcl-XS的表达。EoL-1细胞组成性表达Fas，抗Fas抗体可诱导EoL-1细胞死亡，但Fas/Fas配体系统不参与dbcAMP诱导的EoL-1细胞凋亡。因此，EoL-1细胞系是研究嗜酸性粒细胞白血病细胞分化和凋亡的有用模型。
