Abstract
BackgroundDecreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous β2-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.Methodology/Principal FindingsThirty-two rats were randomly into four groups (n = 8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).Conclusion/SignificanceCompared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis.
Highlights
Asthma is a complex disorder of unknown etiology, characterized by increased bronchial smooth muscle contraction, airway inflammation and tissue remodeling
The ability of nerve growth factor (NGF) to induce differentiated adrenal medullary chromaffin cell (AMCC) to transform into sympathetic neuron is well-documented, and is characterized by observable alterations in morphology and endocrine function
Studies found that glucocorticoid hormones, which antagonize NGF, can block the NGF-induced transformation of AMCCs [3,4,12,13,14,15]
Summary
Asthma is a complex disorder of unknown etiology, characterized by increased bronchial smooth muscle contraction, airway inflammation and tissue remodeling. EPI is secreted by adrenal medullary chromaffin cells (AMCCs), which are derived from the same sympathoadrenal precursor cells that produce neurons. For this reason, AMCCs harbor the potential to transform to the neuron phenotype, and in vitro exposure of AMCCs to nerve growth factor (NGF) can produce this effect [3,4,5]. In our previous studies involving induction of AMCC transformation to neurons in asthmatic rats, we observed decreased EPI and elevated NGF in these animals, and noted that this phenomenon was inhibited by administration of anti-NGF [7,8,9]. An asthmatic model with unilateral adrenalectomy was established in this study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
