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.

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

“…In vitro NGF treatment of eosinophils from patients with allergic bronchial asthma increases viability of these cells, and this effect is correlated to increased expression of the TrkA receptor on eosinophils (Nassenstein et al, 2003). In addition, coculture of lung eosinophils with airway epithelial cells resulted in enhanced epithelial neurotrophin production, as well as in prolonged survival of eosinophils (Hahn et al, 2006).…”

“…Expression of the TrkA receptor was shown on mast cells (Tam et al, 1997), Th2 lymphocytes (Ehrhard et al, 1993a;Lambiase et al, 1997), B lymphocytes (Torcia et al, 1996), eosinophils (Hahn et al, 2006;Nassenstein et al, 2003;Noga et al, 2002), monocytes and macrophages (Ehrhard et al, 1993b;Otten et al, 1994), and basophils (Burgi et al, 1996).…”

Eosinophil-Mediated Cholinergic Nerve Remodeling

“…Allergic inflammation is associated with the release of neurotrophins and other factors that have a direct effect on nerves (1). One effect of inflammatory mediators is that they can alter neuronal neurotransmitter content; this effect is termed neural plasticity.…”

Pharmacology and Therapeutics of Bronchodilators

“…Intriguingly, Lommatzsch et al (2009) showed that unbalanced monotherapy with at least salmeterol in patients with mild asthma increases neurotrophin brain-derived neurotrophic factor production and storage and that increases in airway hyper-responsiveness are associated with this effect. There is increasing evidence that brain-derived neurotrophic factor may enhance airway hyper-responsiveness and eosinophilia in allergic airway inflammation (Nassenstein et al, 2003).…”