Induction of plasminogen activator inhibitor type 2 expression during differentiation of human K562 cells towards a macrophage phenotype

Human K562 cells, a multipotential cell line of hematopoietic origin, were found to differentiate towards a macrophage-like cell when incubated in the presence of phorbol myristate acetate (PMA). Differentiation was accompanied by the expression and secretion of a plasminogen activator inhibitor (PAI). Incubation of the cells in the presence of other agents (dimethyl sulfoxide, retinoic acid, vitamin D3) capable of inducing differentiation towards other phenotypes did not lead to the induction of PAI expression. The inhibitor induced by PMA was partially purified and it exhibited biochemical characteristics similar to PAI-2. The molecule is a glycoprotein with a pI of 5.8. Northern blot analysis of mRNA isolated from control and PMA-treated cells revealed the presence of an approximately 2-kilobase mRNA from treated cells that hybridized to a PAI-2-specific synthetic oligonucleotide. This mRNA did not hybridize with a PAI-I-specific oligonucleotide and was absent from control cells. These observations are consistent with the literature regarding PAI-2 expression by cells of the monocyte-macrophage lineage. Therefore, commitment of this multipotential cell line towards the macrophage lineage results in specific activation of the PAI-2 gene. Further analysis of the regulatory elements of the PAI-2 gene may provide additional insight into the relationship between this gene and the macrophage phenotype.