Induction of aminopeptidase N/CD13 on human lymphocytes after adhesion to fibroblast-like synoviocytes, endothelial cells, epithelial cells, and monocytes/macrophages.

Aminopeptidase N (APN/CD13) is a transmembrane ectoenzyme occurring on a wide variety of cells. In contrast to monocytes and granulocytes, lymphocytes of peripheral blood do not express CD13 Ag. However, tumor-infiltrating T cells in renal cell cancer as well as synovial fluid T cells from patients suffering from various forms of arthritis can be CD13 positive. To learn more about expression of CD13 in these tissues, we cocultured lymphocytes with different adherent cell lines. CD13 expression was induced in T and B lymphocytes upon adhesion to fibroblast-like synoviocytes, HUVEC, renal tubular epithelial cells, and monocytes/macrophages but not always upon interaction with different tumor cell lines. Induction of APN was rapid, occurring as early as 1 h after coincubation. Expression persisted for >3 days and partially resisted inhibition by cycloheximide. Fixation of adherent cells with paraformaldehyde could not prevent induction of CD13 in lymphocytes. Soluble APN from human kidneys or placenta could not induce CD13 expression on lymphocytes. Induction of CD13 Ag on lymphocytes required direct cell-to-cell contact as shown in experiments using dual chambers. Lymphocytes exhibited an induction not only in CD13 protein but also in Ala-pNA-cleaving enzyme activity and in CD13 mRNA. Lymphocytic expression of CD13 represents a potentially increased cellular ability to inactivate inflammatory mediators. Furthermore, CD13 could be involved in adhesion, in lymphocytic migration, or in the Ag processing of peptides bound in the groove of MHC class II molecules.