Modulation of CD157 expression myeloid differentiation in multi-lineage ofpromyelocytic cell lines

CD157/BST-1 is expressed on mature myeloid cells but not on their precursor s in vivo. Also CD38, a homologous gene to CD157, is upregulated in promyel ocytic HL-60 cells by the monocyte and granulocyte differentiation-inducing 1 alpha ,25-dihydroxyvitamin D3 (VD3) and all-trans retinoic acid (ATRA), respectively. We have examined whether CD157 expression is upregulated when the promyeloid HL-60 and/or U937 cells are induced to differentiate into m ature phenotypes in vitro. VD3 treatment irreversibly upregulated the expre ssion of CD157 in HL-60 cells but not in U937 cells in a time- and concentr ation-dependent manner when analyzed by flow cytometry, immunoblotting and/ or RT-PCR. Different monocyte and granulocyte lineage inducers induced CD15 7 expression to varying extents while the macrophage differentiation-induci ng phorbol 12-myristate W-acetate (PMA) induced ifs down-regulation. Time-k inetics of VD3 treatment of HL-60 cells showed that the appearance of CD157 and CD11b (a differentiation marker) antigens were not substantial up to 2 4 hours but increased subsequently although the appearance of CD38 became s ignificant within 6 hours. Two-color staining of VD3-treated HL-60 cells di splayed an apparently linear correlation between CD157 and CD11b, expressio n. Dibutyryl cAMP (cAMP agonist) and forskolin (cAMP-increasing agent) augm ented the VD3 dependent induction of CD157 and CD11b expression while PGE1 (cAMP-decreasing agent) inhibited it, suggesting the involvement of a cAMP- dependent mechanism in VD3-induced CD157 upregulation. Co-treatment of HL-6 0 cells with VD3 plus TNF-alpha or ara-C produced an additive effect on CD1 57 upregulation, The upregulated CD157 in the VD3 differentiated HL-60 cell s was able to activate CD157-dependent tyrosine kinase signal when cross-li nked with anti-CD157 antibody.