INTRACELLULAR CONCENTRATIONS OF INOSITOL, GLYCEROPHOSPHOINOSITOL AND INOSITOL PENTAKISPHOSPHATE INCREASE DURING HEMATOPOIETIC-CELL DIFFERENTIATION

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 D-3. In both cases, differentiation was accompanied by increases in intracellular inositol (Ins), glycerophosphoinositol (GroPIns) and inositol pentakisphosphate (InsP(5)) 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 [InsP(5)] rose later. Similarly, neutrophils derived in culture by the spontaneous differentiation of myeloid blast cells contained increased levels of Ins, GroPIns and InsP(5) 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 InsP(5). We have previously demonstrated increases in Ins, GroPIns and Ins(1,3,4,5,6)P-5 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)P-5 and Ins accumulate during haemopoietic differentiation remain unknown.