title: The vesicular monoamine transporter 2 (VMAT2) is expressed by normal and tumor cutaneous mast cells and Langerhans cells of the skin but is absent from Langerhans cell histiocytosis.
abstract: Monoamine storage in secretory granules is mediated by the vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2). The aim of our study was to identify monoamine-handling normal and neoplastic inflammatory cells in the skin by their expression of VMAT1 and VMAT2. Normal skin from various parts of the body, as well as 21 cases of cutaneous mastocytosis and 10 cases of cutaneous Langerhans cell histiocytosis were analyzed by immunohistochemistry, radioactive in situ hybridization, and double-fluorescence confocal microscopy. VMAT2-positive cells in the subepidermal layer were identified as mast cells by their expression of tryptase. Neoplastic mast cells in all cases of cutaneous mastocytosis retained their VMAT2 positivity. The intraepidermal VMAT2-expressing cells were identified as Langerhans cells by their CD1a positivity. VMAT2 was absent from Langerhans cell histiocytosis. VMAT2 is an excellent marker for normal and neoplastic mast cells. The expression of VMAT2 demonstrates the capacity of mast cells for monoamine storage and handling. The presence of VMAT2 in epidermal Langerhans cells revealed a previously unrecognized monoamine-handling phenotype of these cells and indicates possible involvement of amine storage and release associated with antigen presentation. Absence of VMAT2 in neoplastic Langerhans cells indicates a loss of monoamine handling capacity of these cells during tumorigenesis.
authors.affiliation: Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Marburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Anlauf
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schafer
authors.forename: Candan
authors.initials: C
authors.lastname: Depboylu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartschuh
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
authors.forename: Guenter
authors.initials: G
authors.lastname: Kloppel
authors.forename: Eberhard
authors.initials: E
authors.lastname: Weihe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D015614:Histiocytosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007801:Langerhans Cells / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D034701:Mastocytosis, Cutaneous / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D018613:Microscopy, Confocal; D008875:Middle Aged; D009479:Neuropeptides; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins