PMID- 16630935
OWN - NLM
STAT- MEDLINE
DCOM- 20060531
LR  - 20091119
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 117
IP  - 4
DP  - 2006 Apr
TI  - Airway epithelial cells produce neurotrophins and promote the survival of 
      eosinophils during allergic airway inflammation.
PG  - 787-94
AB  - BACKGROUND: Eosinophil-epithelial cell interactions make a major contribution to 
      asthmatic airway inflammation. Nerve growth factor (NGF), brain-derived 
      neurotrophic factor (BDNF), and other members of the neurotrophin family, 
      originally defined as a class of neuronal growth factors, are now recognized to 
      support the survival and activation of immune cells. Neurotrophin levels are 
      increased in bronchoalveolar lavage fluid during allergic asthma. OBJECTIVE: We 
      sought to investigate the role of neurotrophins as inflammatory mediators in 
      eosinophil-epithelial cell interactions during the allergic immune response. 
      METHODS: Neurotrophin expression in the lung was investigated by means of 
      immunohistochemistry and ELISA in a mouse model of chronic experimental asthma. 
      Coculture experiments were performed with airway epithelial cells and 
      bronchoalveolar lavage fluid eosinophils. RESULTS: Neurotrophin levels increased 
      continuously during chronic allergic airway inflammation, and airway epithelial 
      cells were the major source of NGF and BDNF within the inflamed lung. Epithelial 
      neurotrophin production was upregulated by IL-1beta, TNF-alpha, and T(H)2 
      cytokines. Lung eosinophils expressed the BDNF and NGF receptors 
      tropomyosin-related kinase (Trk) A and TrkB, and coculture with airway epithelial 
      cells resulted in enhanced epithelial neurotrophin production, as well as in 
      prolonged survival of eosinophils. Eosinophil survival was completely abolished 
      in the presence of the neurotrophin receptor Trk antagonist K252a. CONCLUSION: 
      During allergic inflammation, airway epithelial cells express increased amounts 
      of NGF and BDNF that promote the survival of tissue eosinophils. Controlling 
      epithelial neurotrophin production might be an important therapeutic target to 
      prevent allergic airway eosinophilia. CLINICAL IMPLICATIONS: Attenuating the 
      release of inflammatory mediators from the activated airway epithelium will 
      become an important strategy to disrupt the pathogenesis of chronic allergic 
      asthma.
FAU - Hahn, Christian
AU  - Hahn C
AD  - Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the 
      University, Philipps-University Marburg, Germany.
FAU - Islamian, Ariyan Pirayesh
AU  - Islamian AP
FAU - Renz, Harald
AU  - Renz H
FAU - Nockher, Wolfgang Andreas
AU  - Nockher WA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060221
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Asthma/etiology/pathology/physiopathology
MH  - Base Sequence
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cell Survival
MH  - Cytokines/pharmacology
MH  - Eosinophils/*pathology/physiology
MH  - Epithelial Cells/drug effects/physiology
MH  - Female
MH  - Inflammation Mediators/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Biological
MH  - Nerve Growth Factors/*biosynthesis/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, trkA/biosynthesis
MH  - Receptor, trkB/biosynthesis
MH  - Respiratory Hypersensitivity/*pathology/*physiopathology
MH  - Respiratory System/drug effects/*pathology/*physiopathology
EDAT- 2006/04/25 09:00
MHDA- 2006/06/01 09:00
CRDT- 2006/04/25 09:00
PHST- 2005/07/04 00:00 [received]
PHST- 2005/12/05 00:00 [revised]
PHST- 2005/12/21 00:00 [accepted]
PHST- 2006/04/25 09:00 [pubmed]
PHST- 2006/06/01 09:00 [medline]
PHST- 2006/04/25 09:00 [entrez]
AID - S0091-6749(05)04092-3 [pii]
AID - 10.1016/j.jaci.2005.12.1339 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2006 Apr;117(4):787-94. doi: 10.1016/j.jaci.2005.12.1339. 
      Epub 2006 Feb 21.