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

We have analysed the levels of soluble inositol metabolites in HL60 ce lls as they differentiate towards neutrophils in response to a combina tion of all-trans-retinoic acid and granulocyte colony-stimulating fac tor and towards monocytes in response to 1 alpha-25-dihydroxyvitamin D -3. In both cases, differentiation was accompanied by increases in int racellular inositol (Ins), glycerophosphoinositol (GroPIns) and inosit ol pentakisphosphate (InsP(5)) concentrations. [GroPIns] reached a pea k early in the differentiation of both neutrophils and monocytes and s ubsequently fell to about double the starting level as the cells acqui red mature characteristics, and [InsP(5)] rose later. Similarly, neutr ophils derived in culture by the spontaneous differentiation of myeloi d blast cells contained increased levels of Ins, GroPIns and InsP(5) w hen compared to their parental blast cells. We have also compared the inositol metabolites present in two pairs of cell lines which are repr esentative of immature and mature B and T lymphocytes. The mature cell s again contained the higher levels of GroPIns and InsP(5). We have pr eviously 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 obs ervations suggest that deacylation of phosphatidylinositol by a phosph olipase A/lysophospholipase pathway, forming GroPIns and probably also regulatory arachidonate metabolites, has some role in haemopoietic ce ll differentiation. The reasons why Ins(1,3,4,5,6)P-5 and Ins accumula te during haemopoietic differentiation remain unknown.