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

Cell Immunol. 2000 Apr 10;201(1):22-32. doi: 10.1006/cimm.2000.1629.

Abstract

In the present study, we characterized in monocytes the rise in [Ca(2+)](i) evoked by monoclonal antibodies (mAbs) to aminopeptidase N (APN)/CD13, showing a two-phase calcium increase with a small-belled [Ca(2+)](i) rise due to the release of calcium from intracellular stores and a more sustained plateau due to the influx of calcium from the extracellular environment. Tyrosine kinase inhibitors were able to inhibit the rise in [Ca(2+)](i) induced by ligation APN/CD13, as were inhibitors of the phosphatidylinositol 3-kinase. For 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 the influence of APN/CD13 ligation. Although the in vivo ligand as well as possible cooperating membrane molecules remains to be identified, our results suggest that the membrane ectoenzyme APN/CD13 is a novel signal transduction molecule in monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Antibodies, Monoclonal / immunology
  • CD13 Antigens / immunology
  • CD13 Antigens / metabolism*
  • Calcium / metabolism
  • Chromones / pharmacology
  • Genistein / pharmacology
  • Humans
  • Interleukin-8 / genetics
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Morpholines / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proteins / pharmacology
  • RNA, Messenger / metabolism
  • U937 Cells
  • Wortmannin
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Androstadienes
  • Antibodies, Monoclonal
  • Chromones
  • Interleukin-8
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteins
  • RNA, Messenger
  • phosphoprotein phosphatase inhibitor 1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Genistein
  • Protein-Tyrosine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • CD13 Antigens
  • Calcium
  • Wortmannin