title: Modulation of growth relative to division regulates expression of a Theileria annulata infection associated antigen in HL-60 cells differentiating towards granulocytes.
abstract: The protozoan parasite Theileria annulata has the ability to immortalise the bovine leukocyte in which it resides. Immortalisation is known to be associated with a number of molecular and antigenic alterations to the host cell. In this study cells of related lineage were compared with T. annulata infected cells, using a monoclonal antibody which detects an infection associated glycoprotein on the host cell surface. The results show that this antibody recognises a 160 kDa antigen in HL-60 cells, and that expression of this antigen is up-regulated as cells are induced to differentiate towards granulocytes, but not macrophages. Up-regulation was observed to proceed in a quantitative manner, with progression through an intermediate phase, before full antigen expression and granulocyte formation was observed. Limited incubation with inducer (DMSO) for 18 h indicated that intermediate cells could revert to negative cells, while longer exposure resulted in conversion to high level antigen expression and a commitment to differentiate. Alteration of cell culture conditions and modulation of division (DNA synthesis) relative to growth (protein synthesis) by incubation in aphidicolin resulted in an increase in the number of cells expressing antigen at both the intermediate level and the level associated with commitment. Based on these results and related studies we present a model which proposes that differentiation is initiated, and then progresses to a quantitative commitment threshold, by altering the level of key regulators of gene expression relative to their DNA templates.
authors.affiliation: UNIV GLASGOW,DEPT VET PARASITOL,GLASGOW G61 1QH,LANARK,SCOTLAND.
authors.forename: C
authors.initials: C
authors.lastname: Dando
authors.forename: B
authors.initials: B
authors.lastname: Shiels