EXPRESSION OF THE HUMAN NRAMP1 GENE IN PROFESSIONAL PRIMARY PHAGOCYTES - STUDIES IN BLOOD-CELLS AND IN HL-60 PROMYELOCYTIC LEUKEMIA

In the mouse, mutations at the natural resistance-associated macrophag e protein 1 (Nramp1) gene abrogate resistance to infection with antige nically unrelated intracellular parasites such as Mycobacterium, Salmo nella, and Leishmania, Nramp1 expression is restricted to reticuloendo thelial organs and peripheral blood leukocytes, where the protein may function as a membrane transporter of an as yet to be identified subst rate, To identify the human blood cell type(s) expressing NRAMP1 mRNA and determine how Nramp1 expression is regulated in these cells, we ha ve examined separated populations of peripheral blood leukocytes and i n vitro cell lines, We observed that polymorphonuclear leukocytes (PMN ) are the major site of NRAMP1 expression, followed to a lesser degree by monocytes (MN), Migration of MN to tissues (alveolar macrophages) or maturation in vitro dong-term culture) was associated with a higher level of NRAMP1 expression compared with blood MN, Northern analyses of RNA from model cultured cells showed absence of NRAMP1 expression i n transformed cell lines from either erythroid or lymphoid T or B line ages as well as progenitors of the monocyte/macrophage pathway (KG1, U 937, THP1), and the HL-60 promyelocytic leukemia, Induction of differe ntiation of HL-60 cells toward either the monocyte/macrophage (vitamin D3, phorbol ester) or the granulocyte pathways (DMF DMSO), as measure d by induction of IL8-Rb, c-FMS, and CD14 marker gene expression, was concomitant with a strong induction of NRAMP1 expression, These result s suggest that NRAMP1 expression is specific to the myeloid Lineage an d is acquired during the maturation of PMN and MN, The possibility tha t NRAMP1 may be a component of the phagosomal/endosomal apparatus comm on to PMN and MN is discussed.