Mountford J C, Bunce C M, French P J, Michell R H, Brown G
Department of Immunology, University of Birmingham, Edgbaston, UK.
Biochim Biophys Acta. 1994 May 26;1222(1):101-8. doi: 10.1016/0167-4889(94)90030-2.
We have analysed the levels of soluble inositol metabolites in HL60 cells as they differentiate towards neutrophils in response to a combination of all-trans-retinoic acid and granulocyte colony-stimulating factor and towards monocytes in response to 1 alpha-25-dihydroxyvitamin D3. In both cases, differentiation was accompanied by increases in intracellular inositol (Ins), glycerophosphoinositol (GroPIns) and inositol pentakisphosphate (InsP5) concentrations. [GroPIns] reached a peak early in the differentiation of both neutrophils and monocytes and subsequently fell to about double the starting level as the cells acquired mature characteristics, and [InsP5] rose later. Similarly, neutrophils derived in culture by the spontaneous differentiation of myeloid blast cells contained increased levels of Ins, GroPIns and InsP5 when compared to their parental blast cells. We have also compared the inositol metabolites present in two pairs of cell lines which are representative of immature and mature B and T lymphocytes. The mature cells again contained the higher levels of GroPIns and InsP5. We have previously demonstrated increases in Ins, GroPIns and Ins(1,3,4,5,6)P5 levels during the differentiation of HL60 cells towards neutrophils in response to DMSO and of GroPIns during the monocytoid differentiation of normal primitive myeloid blast cells in response to PMA. These observations suggest that deacylation of phosphatidylinositol by a phospholipase A/lysophospholipase pathway, forming GroPIns and probably also regulatory arachidonate metabolites, has some role in haemopoietic cell differentiation. The reasons why Ins(1,3,4,5,6)P5 and Ins accumulate during haemopoietic differentiation remain unknown.
我们分析了HL60细胞在全反式维甲酸和粒细胞集落刺激因子联合作用下向中性粒细胞分化以及在1α-25-二羟基维生素D3作用下向单核细胞分化过程中可溶性肌醇代谢物的水平。在这两种情况下，分化都伴随着细胞内肌醇（Ins）、甘油磷酸肌醇（GroPIns）和肌醇五磷酸（InsP5）浓度的增加。[GroPIns]在中性粒细胞和单核细胞分化早期达到峰值，随后随着细胞获得成熟特征而降至起始水平的两倍左右，而[InsP5]稍后升高。同样，与亲代原始细胞相比，通过髓系原始细胞自发分化在培养中获得的中性粒细胞中Ins、GroPIns和InsP5水平升高。我们还比较了两对分别代表未成熟和成熟B淋巴细胞及T淋巴细胞的细胞系中存在的肌醇代谢物。成熟细胞中GroPIns和InsP5的水平同样更高。我们之前已经证明，HL60细胞在二甲基亚砜作用下向中性粒细胞分化过程中Ins、GroPIns和Ins(1,3,4,5,6)P5水平升高，正常原始髓系原始细胞在佛波酯作用下向单核细胞分化过程中GroPIns水平升高。这些观察结果表明，磷脂酶A/溶血磷脂酶途径使磷脂酰肌醇脱酰基，形成GroPIns以及可能还有具有调节作用的花生四烯酸代谢物，在造血细胞分化中发挥了一定作用。造血分化过程中Ins(1,3,4,5,6)P5和Ins积累的原因仍然未知。
