Universität zu Köln

Peng, Wen-Ming, Maintz, Laura, Allam, Jean-Pierre, Raap, Ulrike, Guetgemann, Ines, Kirfel, Jutta, Wardelmann, Eva, Perner, Sven, Zhao, Wei, Fimmers, Rolf, Walgenbach, Klaus, Oldenburg, Johannes, Schwartz, Lawrence B. and Novak, Natalija (2013). Increased circulating levels of neurotrophins and elevated expression of their high-affinity receptors on skin and gut mast cells in mastocytosis. Blood, 122 (10). S. 1779 - 1789. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

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 tropomyosin-related kinase A (TrkA) for nerve growth factor (NGF)-beta, 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-beta; NT-3; TrkA, TrkB, and TrkC; and isoforms truncated TrkB-T1 and truncated TrkC were observed on skin MCs. Patients with mastocytosis featured elevated serum levels of NGF, NT-3, and NT-4. Levels of NGF-beta and NT-4 correlated with tryptase levels, suggesting a link between MC load and blood levels of NGF and NT-4. Migration of CD117(+) progenitor cells from the blood was enhanced toward NGF-beta 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Peng, Wen-Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Maintz, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Allam, Jean-Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED Raap, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Guetgemann, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirfel, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Wardelmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhao, Wei UNSPECIFIED UNSPECIFIED UNSPECIFIED Fimmers, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Walgenbach, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Oldenburg, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwartz, Lawrence B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Novak, Natalija UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476075
DOI:	10.1182/blood-2012-12-469882
Journal or Publication Title:	Blood
Volume:	122
Number:	10
Page Range:	S. 1779 - 1789
Date:	2013
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NERVE GROWTH-FACTOR; FACTOR PREVENTS APOPTOSIS; HUMAN TRKB GENE; SYSTEMIC MASTOCYTOSIS; TYROSINE KINASE; TRUNCATED TRKB.T1; ATOPIC-DERMATITIS; FUNCTIONAL TRKA; FACTOR NGF; C-KIT Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47607