Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis.
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.
Anlauf
Martin
M
Department of Pathology, University of Kiel, Michaelisstr. 11, 24105 Kiel, Germany. manlauf@path.uni-kiel.de
Schäfer
Martin K-H
MK
Schwark
Thorsten
T
von Wurmb-Schwark
Nicole
N
Brand
Viktoria
V
Sipos
Bence
B
Horny
Hans-Peter
HP
Parwaresch
Reza
R
Hartschuh
Wolfgang
W
Eiden
Lee E
LE
Klöppel
Günter
G
Weihe
Eberhard
E
D000818:Animals; D001491:Basophils / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001792:Blood Platelets / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D006410:Hematopoiesis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007801:Langerhans Cells / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008253:Macaca mulatta; D008407:Mast Cells / Q000378:metabolism; D034721:Mastocytosis, Systemic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008533:Megakaryocytes / Q000378:metabolism; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins