REGULATION AND SPECIFICITY OF MNDA EXPRESSION IN MONOCYTES, MACROPHAGES, AND LEUKEMIA-B LYMPHOMA CELL-LINES

The expression of the human myeloid cell nuclear differentiation antig en (MNDA) was observed specifically in cells of the granulocyte-macrop hage lineage in our earlier reports. The specificity of MNDA expressio n for cells in the granulocyte-macrophage lineage was reexamined in ce ll lines established from patients with Philadelphia chromosome-positi ve chronic myeloid leukemia. Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation coul d be induced in vitro, while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA. Cells originating from cases of Burkitt's lymphoma were negative. By contras t, three lymphoblastoid cell lines (immortalized in vitro with Epstein -Barr virus) were weakly positive and MN DA was up-regulated by interf eron-alpha (IFN-alpha) treatment. As we reported previously, MNDA mRNA level in adherent monocytes is elevated by IFN-alpha; in this study, we further assessed MNDA expression in in vitro monocyte-derived macro phages. Three additional agents (endotoxin, phytohemagglutinin, and ph orbol ester) and other conditions that affect function, cytokine produ ction, differentiation, and/or growth of monocytes were examined for t heir ability to alter MNDA expression. The results varied with the age nt, cell type, and stage of differentiation. Changes in MNDA expressio n occurred slowly (hours to days), suggesting that MNDA could mediate changes realized over a long period. The results also reveal a discord ance in certain MNDA positive cells between steady-state levels or cha nges in levels of protein and mRNA indicating that the regulation of M NDA expression occurs at more than one point. Changes in MNDA expressi on are consistent with a role in opposing macrophage differentiation a nd activation of monocytes/macrophages. (C) 1994 Wiley-Liss, Inc.