A role for urokinase in mediating phorbol ester induced macrophagelike maturation and adhesion of u937 and other myeloid cells

The phorbol ester, phorbol myristate acetate (PMA), induces myeloid cells to differentiate towards the macrophage lineage. Polyclonal antibodies to the urokinase plasminogen activator (u-PA) interfere with this process as defined by the inability of U937 cells to adhere on tissue culture surfaces. This block in differentiation is overcome by a 21 amino acid synthetic peptide from the u-PA growth factor domain which has residues of the receptor binding sequence. Moreover, a 40 amino acid peptide from the u-PA growth factor domain is more potent and enhances by 4-fold the PMA stimulated adhesion of a similar cell line, HL60. These observations indicate that the growth factor domain of u-PA plays an important role in PMA mediated myeloid cell differentiation and adhesion.