From the Authors:
We thank Dr. Wang and colleagues for their thoughtful letter and excellent points regarding the potential importance of brain-derived neurotrophic factor (BDNF) in asthma, as well as its cellular source. We are in clear agreement that this (and earlier studies) suggest further study of neurotrophins in asthma is needed.
Regarding the cellular source, Wang and colleagues previously showed Ca2+-dependent regulation of BDNF secretion in human airway smooth muscle (ASM) (1). In contrast, we focused on epithelial cells and did not address ASM expression. However, we did find robust mRNA and protein expression in pure cultures of human airway epithelial cells, supporting at least some contribution from these cells. Further, although ASM could certainly contribute, we believe that the close proximity of epithelial cells to the airway lumen (and the sputum collection) make human airway epithelial cells the more likely source. The correlation of BDNF levels with airway hyperresponsiveness observed in our study (2) supports an effect of BDNF on airway hyperresponsiveness but, unfortunately, does not help determine a source.
However, in prior murine studies, BDNF was more strongly expressed in bronchial epithelial cells, while moderately expressed in ASM, being further enhanced in the epithelium after allergen challenge (3–5). According to these reports, we immunostained for BDNF (Santa Cruz Biotechnology, Santa Cruz, CA) on human tissue from one healthy subject and one patient with severe asthma. BDNF staining was observed in the bronchial epithelial layer and a few inflammatory cells (likely eosinophils or mast cells). The intensity of BDNF staining in the epithelium of the patient with severe asthma was greater than in the healthy control subject (6), whereas minimal staining was observed in either subject’s ASM, suggesting epithelial cells may be a more prominent source. However, much more study is clearly needed.
Thus, we agree that the main cellular source for BDNF in human asthmatic airways remains to be determined and that further studies of this fascinating pathway in human disease are urgently needed.
Footnotes
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
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