TY - JOUR
T1 - Increased circulating levels of neurotrophins and elevated expression of their high-Affinity receptors on skin and gut mast cells in mastocytosis
AU - Peng, Wen Ming
AU - Maintz, Laura
AU - Allam, Jean Pierre
AU - Raap, Ulrike
AU - Gutgemann, Ines
AU - Kirfel, Jutta
AU - Wardelmann, Eva
AU - Perner, Sven
AU - Zhao, Wei
AU - Fimmers, Rolf
AU - Walgenbach, Klaus
AU - Oldenburg, Johannes
AU - Schwartz, Lawrence B.
AU - Novak, Natalija
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - Mastocytosis is a rare heterogeneous disease characterized by increase of mast cells (MCs) in different organs. Neurotrophins (NTs) have been shown to promote differentiation and survival of MCs, which in turn represent a major source of NTs. Thus, a contribution of NTs to mastocytosis seems highly conceivable but has not yet been investigated.We could demonstrate expression of high-Affinity NT receptors tropomyosinrelated kinase A (TrkA) for nerve growth factor (NGF)-b, TrkB for brain-derived neurotrophic factor, and NT-4 and TrkC for NT-3 on skin MCs; and of TrkA and TrkC on intestinal MCs of patients with mastocytosis. Moreover, increased expression of NGF-b; NT-3; TrkA, TrkB, and TrkC; and isoforms truncated TrkB-T1 and truncated TrkC were observed on skinMCs. Patients with mastocytosis featured elevated serum levels of NGF, NT-3, and NT-4. Levels of NGF-b and NT-4 correlated with tryptase levels, suggesting a link betweenMCload and blood levels of NGF and NT-4. Migration of CD1171 progenitor cells from the blood was enhanced toward NGF-b gradient in both mastocytosis and controls. Together with enhanced NT levels, the elevated expression of modified Trk receptors on skin and gut MCs might contribute to the pathophysiology of mastocytosis in autocrine and paracrine loops.
AB - Mastocytosis is a rare heterogeneous disease characterized by increase of mast cells (MCs) in different organs. Neurotrophins (NTs) have been shown to promote differentiation and survival of MCs, which in turn represent a major source of NTs. Thus, a contribution of NTs to mastocytosis seems highly conceivable but has not yet been investigated.We could demonstrate expression of high-Affinity NT receptors tropomyosinrelated kinase A (TrkA) for nerve growth factor (NGF)-b, TrkB for brain-derived neurotrophic factor, and NT-4 and TrkC for NT-3 on skin MCs; and of TrkA and TrkC on intestinal MCs of patients with mastocytosis. Moreover, increased expression of NGF-b; NT-3; TrkA, TrkB, and TrkC; and isoforms truncated TrkB-T1 and truncated TrkC were observed on skinMCs. Patients with mastocytosis featured elevated serum levels of NGF, NT-3, and NT-4. Levels of NGF-b and NT-4 correlated with tryptase levels, suggesting a link betweenMCload and blood levels of NGF and NT-4. Migration of CD1171 progenitor cells from the blood was enhanced toward NGF-b gradient in both mastocytosis and controls. Together with enhanced NT levels, the elevated expression of modified Trk receptors on skin and gut MCs might contribute to the pathophysiology of mastocytosis in autocrine and paracrine loops.
UR - http://www.scopus.com/inward/record.url?scp=84886475920&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-12-469882
DO - 10.1182/blood-2012-12-469882
M3 - Journal articles
C2 - 23869086
AN - SCOPUS:84886475920
SN - 0006-4971
VL - 122
SP - 1779
EP - 1788
JO - Blood
JF - Blood
IS - 10
ER -
