Neurotrophins and Neurotrophin Receptors in Human Pulmonary Arteries

Abstract

The localization of neurotrophins (NTs) and NT receptors was analyzed in sections of human extra- and intrapulmonary arteries by Western blot analysis and immunohistochemistry. In extrapulmonary branches of human pulmonary artery, NT and NT receptor immunoreactivity was located in the tunica intima, within endothelium, in the tunica media, within smooth muscle and in the tunica adventitia. In different sized intrapulmonary arteries, NT and NT receptor immunoreactivity was observed primarily in the tunica adventitia. A faint NT and NT receptor immunoreactivity was observed in the tunica media of large-sized branches of intrapulmonary arteries, but not within medium- or small-sized intrapulmonary vessels or in tunica intima of different sized intrapulmonary arteries. These findings suggest that NTs may have a role in the control of vascular responses in the pulmonary system acting as local paracrine or autocrine mediators. The possible relevance of the NT system in human pulmonary vasculature identified in this study is discussed.

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

“…Expression of TrkA protein was then shown by immunohistochemistry in isolated human alveolar macrophages (Ricci et al, 2000b), in isolated extrapulmonary arteries (Ricci et al, 2000a), and was later also evidenced on human airway and vascular smooth muscles, on alveolar cells, on airway sensory nerves, as well as on infiltrated inflammatory cells, in particular macrophages, mast cells and lymphocytes (Kassel et al, 2001;Olgart Hoglund et al, 2002;Ricci et al, 2004b). Similar TrkA expression was shown in the mouse lung (Hikawa et al, 2002;Nassenstein et al, 2006).…”

“…Neurotrophins and their receptors are expressed on pulmonary arteries (Ricci et al, 2000a), and their expression is increased in the lung of spontaneously hypertensive rats (Ricci et al, 2004a). A role for neurotrophins in the control of the pulmonary arterial tone was recently proposed, through activation of the p75 NTR receptor (Xu et al, 2008).…”

Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells

“…Neurotrophins (BDNF) have been shown to be expressed by some, but not all, endothelial cells in culture (6,8,43). Using brain-derived, immortalized endothelial cells (RBE4 cells) we determined that these cells indeed express BDNF in our threedimensional culture system and that expression is increased following hypoxic treatment (Fig.…”

“…In recent studies we and others have (3,4) shown that selected angiogenic factors, VEGF 1 in particular, are capable of not only affecting a variety of endothelial behaviors but also are capable of affecting neuronal behavior in a receptor-specific fashion. Interestingly, recent studies have demonstrated that neurotrophins expressed by endothelia and are capable of influencing several endothelial cell functions including endothelial cell survival and vessel stabilization (5)(6)(7) and that endothelial cells may express neurotrophin receptors (8).…”

Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

“…Neurotrophins have also been detected within vascular endothelial cells [123], and neurotrophin receptors are expressed on the intima and adventitia [124]. Neurotrophins have been found to promote endothelial barrier permeability, plasma extravasation, cellular infiltration, and the release of pro-inflammatory cytokines [125].…”