title: The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma.
abstract: Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of neurotrophins on eosinophil function in allergic asthma. Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.
authors.affiliation: Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Nassenstein
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.forename: Veit Johannes
authors.initials: VJ
authors.lastname: Erpenbeck
authors.forename: Marek
authors.initials: M
authors.lastname: Lommatzsch
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schmidt
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Werner
authors.initials: W
authors.lastname: Luttmann
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
authors.forename: Johann Christian
authors.initials: JC
authors.lastname: Virchow
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D020933:Neurotrophin 3 / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019208:Brain-Derived Neurotrophic Factor; D037181:Lectins, C-Type; D020932:Nerve Growth Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor; D000099192:CD69 Antigens; C073922:neurotrophin 4