Published ahead of print on June 5, 2003, doi:10.1165/rcmb.2002-0110OC
Am. J. Respir. Cell Mol. Biol., Volume 30, Number 1, January 2004, 12-19
A more recent version of this article appeared on January 1, 2004
Submitted on July 22, 2002
Revised on June 3, 2003
Neurotrophin and neurotrophin receptor protein expression in the human lung
Alberto Ricci1*, Laura Felici1, Salvatore Mariotta1, Francesco Mannino1, Giovanni Schmid1, Claudio Terzano1, Giuseppe Cardillo2, Francesco Amenta3, and Elena Bronzetti1
1 Dipartimento di Scienze Cardiovascolari e Respiratorie, Universita di Roma La Sapienza, Rome, Italy,
2 Unita Operativa di Chirurgia Toracica, Ospedale Carlo Forlanini, Rome, Italy,
3 Dipartimento di Farmacologia e Medicina Sperimentale, Universita di Camerino, Camerino, Italy
* To whom correspondence should be addressed. 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 lung synthesize and release NTs which are probably involved in the pathophysiology of pulmonary disturbances. In this work the expression and anatomical localization of NGF, BDNF 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 (RT-PCR), Western blot and immunohistochemistry. NTs and their cognate receptor mRNA and protein transcripts were detected by RT-PCR and immunoblotting respectively, being NGF and BDNF mRNA and corresponding protein transcripts 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. Microanatomical analysis of immunohistochemical study revealed that bronchial epithelial cells were immunoreactive for different NTs, with a higher intensity of BDNF immune staining compared to 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 broncho-pulmonary tree. An obvious immunoreactivity for NTs and NT receptor protein was also observed in intrapulmonary branches of pulmonary artery. Pulmonary lymphocytes and macrophages express NGF 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.
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