Neurotrophin and Neurotrophin Receptor Protein Expression in the Human Lung

Abstract

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.

Immunohistochemical profile of neurotrophins in human cranial dura mater and meningiomas

“…The data described above confirmed our previous experimental findings (8)(9)(10)(11), hence improving our knowledge on the role of the neurotrophins in the regulation of the meningeal microenvironment and their direct participation in the neoplastic transformation and cellular survival, both essential aspects of the malignant development.…”

“…A definite role of NTs in the dural and leptomeningeal compartments is not well ascertained but a previous study on the expression of mRNAs for NTs revealed high levels of NT3 and NGF in the normal rat dura mater (7). Our observations on the localization and possible roles in different non-neuronal tissues such as lymphoid, lung and prostate (8)(9)(10)(11) encouraged us to persist in our experimental investigations in order to find a possible involvement of NTs in dura mater, both in physiological and pathological conditions (meningiomas).…”

Nerve Growth Factor and Neurotrophin-3 Mediate Survival of Pulmonary Plasma Cells during the Allergic Airway Inflammation

“…Local inhibition of the TrkA receptor and consecutive blocking of NGF signaling may either directly lead to the apoptosis of pulmonary PC, or it may act indirectly via other TrkA-expressing inflammatory cells such as T cells (19) and eosinophils (32) and thus prevent the regulation of other extrinsic factors. In support of this, a previous study shows that reduction of NGF levels leads to a significant reduction of IL-4 levels and prevents the development of airway hyperresponsiveness in OVA-sensitized mice (33).…”

Methylation adjacent to negatively regulating AP-1 site reactivates TrkA gene expression during cancer progression

“…The binding of NGF to TrkA induces phosphorylation of an intracellular tyrosine kinase and activation of signaling pathways that, in turn, induce numerous biologic effects (Hempstead et al, 1991;Bothwell, 1995;Barrett, 2000). NGF and its receptors are expressed in neural tumors like neuroblastoma (Nakagawara et al, 1992;Suzuki et al, 1993) and glioma (Eberhart et al, 2001) and also in nonneural tumors like prostate (George et al, 1998), breast (Descamps et al, 2001), lung (Ricci et al, 2004), and pancreatic cancers (Zhu et al, 2002), suggesting that the NGF-TrkA signaling system is frequently involved in cell migration, growth, and survival during cancer progression. Although reports are not consistent, immunohistochemical studies have revealed that TrkA expression is observed mainly in the cytoplasm of pancreatic cancer cells, whereas intense NGF and p75 NGFR expression is observed in the peripheral nerve (Miknyoczki et al, 1999;Zhu et al, 1999;Sakamoto et al, 2001).…”