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Neurotrophin and Neurotrophin Receptor Protein Expression in the Human Lung

Dipartimento di Scienze Cardiovascolari e Respiratorie, Università di Roma La Sapienza, Rome; Unità Operativa di Chirurgia Toracica, Ospedale Carlo Forlanini, Rome; and Dipartimento di Farmacologia e Medicina Sperimentale, Università di Camerino, Camerino, Italy

Address correspondence to: Alberto Ricci, M.D., Dipartimento di Scienze Cardiovascolari e Respiratorie, Università di Roma La Sapienza, Ospedale Sant'Andrea, Via di Grottarossa, 1035–1039, 00189 Roma, Italy. E-mail: alberto.ricci{at}uniroma1.it

Neurotrophins (NTs) promote survival and differentiation of central and peripheral neurons, and display several activities also in non-neuronal cells. Human lungs synthesize and release NTs, which are probably involved in the pathophysiology of pulmonary disturbances. In this article the expression and anatomic localization of nerve growth factor, brain-derived neurotrophic factor, and NT-3 and of corresponding high-affinity receptors TrkA, TrkB (full-length and truncated [TR-] isoforms), TrkC, and of the low-affinity p75 receptor, were assessed in surgical samples from adult human lung by reverse transcriptase–polymerase chain reaction, Western blot, and immunohistochemistry. NTs and their cognate receptor mRNA and protein transcripts were detected by reverse transcriptase–polymerase chain reaction and immunoblotting, respectively, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA and corresponding protein transcripts being the most expressed. High levels of TrkB-[TR-] mRNA and of its protein transcript were also demonstrated, whereas a low expression of p75 mRNA and of corresponding protein transcript were found. Microanatomic analysis of immunohistochemical study revealed that bronchial epithelial cells were immunoreactive for different NTs, with a higher intensity of BDNF immune staining compared with other NTs, but did not express NT receptor immunoreactivity. Alveolar cells were immunoreactive for TrkA and TrkC receptor protein, but did not display immunoreactivity for NTs or other receptors investigated. Gland cells expressed NT and high-affinity NT receptor immunoreactivity, but not p75 receptor immunoreactivity. NT and low-affinity receptor immunoreactivity was observed within neurons and satellite cells of parasympathetic ganglia as well as in nerve fiber–like structures supplying the bronchopulmonary tree. An obvious immunoreactivity for NTs and NT receptor protein was also observed in intrapulmonary branches of pulmonary artery. Pulmonary lymphocytes and macrophages express nerve growth factor and high-affinity NT receptor immunoreactivity. The role of NTs in non-neuronal tissue including lung has not been clarified yet. The widespread expression of NTs and their receptors in different components of the lung suggests that these factors may contribute to regulate cell function in human lung.

Abbreviations: bronchus-associated lymphoid tissue, BALT • brain-derived neurotrophic factor, BDNF • nerve growth factor, NGF • neurotrophins, NTs • reverse transcriptase–polymerase chain reaction, RT-PCR

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