Aminopeptidase N/CD13 is directly linked to signal transduction pathways in monocytes

In the present study, we characterized in monocytes the rise in [Ca2+](i) e voked by monoclonal antibodies (mAbs) to aminopeptidase N (APN)/CD13, showi ng a two-phase calcium increase with a small-belied [Ca2+](i) rise due to t he release of calcium from intracellular stores and a more sustained platea u due to the influx of calcium from the extracellular environment. Tyrosine kinase inhibitors were able to inhibit the rise in [Ca2+](i) induced by li gation APN/CD13, as were inhibitors of the phosphatidylinositol 3-kinase. F or the first time we can show that mAbs to APN/CD13 provoke phosphorylation of the mitogen-activated protein kinases ERK1/2, JNK, and p38. Furthermore , we show that mRNA of the chemotactic cytokine IL-8 is upregulated under t he influence of APN/CD13 ligation. Although the in vivo ligand as well as p ossible cooperating membrane molecules remains to be identified, our result s suggest that the membrane ectoenzyme APN/CD13 is a novel signal transduct ion molecule in monocytes. (C) 2000 Academic Press.