Increased lymphocytic aminopeptidase N/CD13 promoter activity after cell-cell contact

Aminopeptidase N (APN)/CD13 is a transmembrane ectoenzyme expressed on a wi de variety of cells. With respect to haematopoietic cells, APN/CD13 has bee n considered specific for the myeloid lineage, because granulocytes and mon ocytes/macrophages, but not lymphocytes of peripheral blood, show a surface expression of CD13 antigen. However, we could recently show that cell-cell contact of lymphocytes with endothelial cells, monocytes, and fibroblast-l ike synoviocytes (SFCs) results in an increase of steady-state APN/CD13 mRN A and a rapid expression of cell-surface protein on the lymphocytes. In thi s study using the Dual-Luciferase reporter assay, we demonstrate that inter action of the T-cell line Jurkat with SFCs results in a higher activity of the APN/CD13 myeloid promoter in T cells. An enhancer located between the m yeloid and epithelial APN/CD13 promoter increases the response of the promo ter to the cell-cell contact-induced expression of APN/CD13 in lymphocytes, Adhesion of lymphocytes to extracellular matrix did not result in increase d promoter activity. The lymphocytic promoter response induced by direct ce ll-cell contact with SFCs is not affected by mutations of a proximal promot er element (nucleotides -48 to -35), which has a possible functional role i n the basal APN/CD13 gene expression in lymphocytes. Upregulated peptidase- promoter activity via cell-cell contact shown in this study for the first t ime is discussed as a general mechanism in peptidase induction, (C) 2000 Wi ley-Liss, Inc.