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Vesicular Monoamine Transporter 2 (VMAT2) Expression in Hematopoietic Cells and in Patients with Systemic Mastocytosis

Martin Anlauf, Martin K.-H. Schäfer, Thorsten Schwark, Nicole von Wurmb-Schwark, Viktoria Brand, Bence Sipos, Hans-Peter Horny, Reza Parwaresch, Wolfgang Hartschuh, Lee E. Eiden, Günter Klöppel and Eberhard Weihe

Department of Pathology (MA,VB,BS,GK), Department of Anatomy and Department of Forensic Medicine (TS,NvW-S), and Department of Hematopathology (RP), University of Kiel, Germany; Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, University of Marburg, Germany (MA,MK-HS,EW); Department of Pathology, University of Lübeck, Germany (H-PH); Department of Dermatology, University of Heidelberg, Germany (WH); Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland (LEE)

Correspondence to: Martin Anlauf, MD, Department of Pathology, University of Kiel, Michaelisstr. 11, 24105 Kiel, Germany. E-mail: manlauf{at}path.uni-kiel.de

Uptake of monoamines into secretory granules is mediated by the vesicular monoamine transporters VMAT1 and VMAT2. In this study, we analyzed their expression in inflammatory and hematopoietic cells and in patients suffering from systemic mastocytosis (SM) and chronic myelogenous leukemia (CML). Normal human and monkey tissue specimens and tissues from patients suffering from SM and CML were analyzed by means of immunohistochemistry, radioactive in situ hybridization, real time RT-PCR, double fluorescence confocal laser scanning microscopy, and immunoelectron microscopy. In normal tissue specimens, VMAT2, but not VMAT1, was expressed in mast cells, megakaryocytes, thrombocytes, basophil granulocytes, and cutaneous Langerhans cells. Further hematopoietic and lymphoid cells showed no expression of VMATs. VMAT2 was expressed in all types of SM, as indicated by coexpression with the mast cell marker tryptase. In CML, VMAT2 expression was retained in neoplastic megakaryocytes and basophil granulocytes. In conclusion, the identification of VMAT2 in mast cells, megakaryocytes, thrombocytes, basophil granulocytes, and cutaneous Langerhans cells provides evidence that these cells possess molecular mechanisms for monoamine storage and handling. VMAT2 identifies normal and neoplastic mast cells, megakaryocytes, and basophil granulocytes and may therefore become a valuable tool for the diagnosis of mastocytosis and malignant systemic diseases involving megakaryocytes and basophil granulocytes. (J Histochem Cytochem 54:201–213, 2006)

Key Words: chronic myeloproliferative disease • histamine • mast cell • mastocytosis • tryptase • vesicular monoamine transporter

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