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

Martin Anlauf ^1*, Martin K.-H. Schäfer ¹, Thorsten Schwark ¹, Nicole von Wurmb-Schwark ¹, Viktoria Brand ¹, Bence Sipos ¹, Hans-Peter Horny ¹, Reza Parwaresch ¹, Wolfgang Hartschuh ¹, Lee E. Eiden ¹, Günter Klöppel ¹ and Eberhard Weihe ¹

¹ Department of Pathology (MA,VB,BS,GK), Department of Anatomy and Department of Forensic Medicine (TS,NvW-S), Department of Hematopathology (RP), University of Kiel, Germany; Department of Molecular Neuroscience (MA,MK-HS,EW), Institute of Anatomy and Cell Biology, University of Marburg, Germany; Department of Pathology (H-PH), University of Lübeck, Germany; Department of Dermatology (WH), University of Heidelberg, Germany; and Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation (LEE), NIMH, Bethesda, Maryland

^* To whom correspondence should be addressed. E-mail: manlauf{at}path.uni-kiel.de.

Submitted on May 21, 2005
Accepted on 1 August 2005

	Abstract

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 hemotopoietic 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.

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

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