用视黄酸和1α,25-二羟基维生素D3的各种组合处理HL60细胞，会导致其向中性粒细胞或单核细胞分化，或者无法分化并发生凋亡。

Treatment of HL60 cells with various combinations of retinoids and 1 alpha,25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis.

作者信息

Bunce C M, Wallington L A, Harrison P, Williams G R, Brown G

机构信息

Department of Immunology, University of Birmingham, Edgbaston, UK.

出版信息

Leukemia. 1995 Mar;9(3):410-8.

PMID:7885039

Abstract

It is well documented that treatment of serum-grown HL60 cells with 10(-7) M all-trans retinoic acid (all-trans RA) induces neutrophil differentiation, whereas treatment with 10(-7) M 1 alpha,25 dihydroxyvitamin D3(D3) induces differentiation towards monocytes. In recent investigations, using serum-free grown HL60 cells, we observed that all-trans RA, at 10(-7) M, did not induce neutrophil differentiation and that all-trans RA, at 10(-8) M, reduced the D3 concentration required for monocyte differentiation to 5 x 10(-9) M. In this study, co-operative interactions between all-trans and 9-cis RA and D3 which promote neutrophil and monocyte differentiation of HL60 cells have been analysed in detail. Treatment of serum-free grown HL60 cells with 5 x 10(-7) M all-trans RA or 9-cis RA resulted in sub-optimal neutrophil differentiation (up to 25% mature cells). As shown for all-trans RA, 9-cis RA cooperated with D3 to promote monocyte differentiation. Culture of HL60 cells in 5 x 10(-7) M 9-cis RA together with a wide range of concentrations of D3 resulted in promotion of neutrophil differentiation at 10(-15)-10(-12) D3, a failure to differentiate and apoptosis at 10(-11)-10(-10) M D3, followed by co-operativity between 9-cis RA and 5 x 10(-9) M D3 in inducing monocyte differentiation in the absence of neutrophil differentiation. Similar results were obtained when HL60 cells were treated with 5 x 10(-7) all-trans RA together with a wide range of concentrations of D3. Cross titration analyses of the effects of 9-cis RA and D3 on HL60 cell differentiation were undertaken to determine the boundaries of the concentrations of each agent, alone and in combination, that give rise to optimal neutrophil and monocyte differentiation of HL60 cells. The observed cooperativities between either 9-cis RA or all-trans RA and D3 have important implications for the use of combinations of these agents in differentiation therapy.

摘要

有充分文献记载，用10⁻⁷M全反式维甲酸（全反式RA）处理血清培养的HL60细胞可诱导中性粒细胞分化，而用10⁻⁷M 1α,25-二羟基维生素D3（D3）处理则诱导其向单核细胞分化。在最近的研究中，我们使用无血清培养的HL60细胞观察到，10⁻⁷M的全反式RA不会诱导中性粒细胞分化，而10⁻⁸M的全反式RA可将单核细胞分化所需的D3浓度降至5×10⁻⁹M。在本研究中，我们详细分析了全反式和9-顺式RA与D3之间促进HL60细胞中性粒细胞和单核细胞分化的协同相互作用。用5×10⁻⁷M全反式RA或9-顺式RA处理无血清培养的HL60细胞，导致中性粒细胞分化未达最佳水平（成熟细胞最多25%）。如全反式RA所示，9-顺式RA与D3协同促进单核细胞分化。将HL60细胞在5×10⁻⁷M 9-顺式RA中与多种浓度的D3一起培养，结果显示在10⁻¹⁵ - 10⁻¹²M D3时促进中性粒细胞分化，在10⁻¹¹ - 10⁻¹⁰M D3时无法分化并发生凋亡，随后在无中性粒细胞分化的情况下，9-顺式RA与5×10⁻⁹M D3协同诱导单核细胞分化。当用5×10⁻⁷全反式RA与多种浓度的D3处理HL60细胞时，也得到了类似结果。进行了9-顺式RA和D3对HL60细胞分化影响的交叉滴定分析，以确定每种试剂单独和联合使用时导致HL60细胞最佳中性粒细胞和单核细胞分化的浓度界限。观察到的9-顺式RA或全反式RA与D3之间的协同作用对于在分化治疗中使用这些试剂的组合具有重要意义。