The responses of pulmonary neuroendocrine cells in the lungs of Rana ridibunda to different experimental conditions

The study investigated the localisation and immunohistochemistry of neuroendocrine cells (PNECs) and their behaviour in the lungs of Rana ridibunda under experimental conditions and compared with control lungs. Serotonin- and bombesin-immunoreactive (IR) PNECs were observed as solitary cells or clusters of cells at the base of ciliated epithelium on the dilated apical parts of primary septa where incoming air first arrives, and in the respiratory epithelium. Serotonin-IR PNECs were predominantly present in the ciliated epithelium while bombesin-IR PNECs were found in the ciliated and respiratory epithelium. Additionally, bombesin-IR nerve fibres were found in the epithelium and among smooth muscle cells in the connective tissue. In frogs kept in a dry aquarium, serotonin- and bombesin-IR PNECs were characterised by various stages of secretion. Serotonin-IR PNECs released most of their secretory material, while bombesin-IR PNECs were stimulated for secretion. Moreover. bombesin secretions were raised. In conclusion, the cells were identified as members of the pulmonary epithelial endocrine system and can contribute to the pulmonary biology through a paracrine/endocrine pathway in the lungs of R. ridibunda

Exposure of Dunaliella tertiolecta to lead and aluminum: Toxicity and effects on ultrastructure

The growth response of the marine alga Dunaliella tertiolecta to different concentrations of lead and aluminum was investigated. Both metals had a stimulatory effect at low concentration and an inhibitory effect at high concentration (hormesis). The IC25 values of lead are 8.43, 7.29, and 6.74 mg L-1 for 24, 48, and 72 h, respectively. The corresponding values for aluminum are 30.54, 22.42, and 18.16 mg L-1. Although it seems that the two metals are not directly toxic to the alga at the concentrations found in the environment, as implied by the IC25 values and the environmental concentrations of the metals, low concentrations of both metals, alone and in combination, affected the ultrastructure. The growth of batch-grown cells exposed to 0.5 mg L-1 lead and aluminum, alone and combined, during the 24-h exponential phase was investigated. The same cells were also examined under an electron microscope to determine the biological effects of the two metals on the ultrastructure. The most obvious effects of lead were disrupted thylakoidal membranes, accumulated polyphosphate bodies and vacuoles, and lead precipitates on the cell surface. These ultrastructural alterations were partially present in aluminum-treated and lead-aluminum-treated cells. In joint exposure, the most important change was the lysis of the cell membrane. Aluminum and lead seem to act synergistically on the cell membrane leading to cell membrane lysis

A matter of regeneration and repair: caspases as the key molecules

Researchers have been focused on understanding the pathogenesis of human diseases. They have been working to find the roles of caspases in the balance between apoptosis, autophagy, pyroptosis, and necroptosis, and also in the regeneration of damaged tissue. At this point, besides their death-inducing roles, new findings indicate the role of caspases in proliferation for maintaining the viability of cells in response to signals from apoptotic cells. Recently, determining cell fate has also been identified among other functions of caspases. Findings indicate that caspases direct cellular pathways to cell differentiation by suppressing stem cell self-renewal. The common opinion about the related mechanism is that low and transient caspase activation leads to terminal differentiation by affecting the expression of key genes related to differentiation. Moreover, caspases are essential proteases in the regulation and modulation of the repair process. In repair, they have roles in apoptosis, release of inflammatory cytokines and chemokines, promotion of cell migration, and immune cell infiltration. However, paracrine signaling through caspase activation leads to cell proliferation after cancer therapy and causes tumor relapse, which complicates the current therapy. In this scope, we have reviewed the main mechanisms of pathological, regenerative, and restorative effects of caspases

Neurotrophin-4 dependency of intraepithelial vagal sensory nerve terminals that selectively contact pulmonary NEBs in mice

Important physiological functions of neurotrophins (NTs) in airways and lungs are the early development, differentiation and maintenance of peripheral sensory neurons. The main pulmonary sensory innervation is of vagal origin, with several nerve fibre populations that selectively contact complex morphologically well-characterized receptor end-organs, called neuroepithelial bodies (NEBs). NEBs in mouse lungs are innervated by at least two separate myelinated vagal sensory nerve fibre populations, of which the neurochemical coding is suggestive of a mechanosensory function. Since neurotrophin-4 (NT-4) has been especially described to be important for the maintenance of mechanosensory nerve terminals, the present study aimed at investigating the NT-4 dependency of the two myelinated vagal sensory nerve fibre populations innervating mouse pulmonary NEBs. Multiple immunostaining in 21-day-old and adult mouse lungs revealed the expression of the NT-4 receptor TrkB on the two different myelinated vagal sensory nerve fibre populations, i.e., the vesicular glutamate transporter/calbindin-positive and the P2X2/3- positive fibres, which selectively contact pulmonary NEBs. Examination of the effect of the lack of NT-4 on these NEB-related nerve fibre populations, by comparing adult NT-4-/- and wild-type mice, revealed that in NT-4-/- mice the percentage of NEBs contacted by P2X2/3+ is reduced by 75%, while the VGLUT+/CB+ population seemed to be unaffected. This study demonstrated that although mouse pulmonary NEBs are contacted by two distinct TrkB expressing populations of vagal myelinated afferents, only one is distinctly reduced in NT-4 deficient mice, suggesting the involvement of NTs. In view of the growing evidence for the involvement of NTs in neuronal plasticity associated with airway diseases, pulmonary NEBs innervated by NT-sensitive vagal afferents may play a significant role

Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs

As best characterized for rats, it is clear that pulmonary neuroepithelial bodies (NEBs) are contacted by a plethora of nerve fiber populations, suggesting that they represent an extensive group of multifunctional intraepithelial airway receptors. Because of the importance of genetically modified mice for functional studies, and the current lack of data, the main aim of the present study was to achieve a detailed analysis of the origin and neurochemical properties of nerve terminals associated with NEBs in mouse lungs. Antibodies against known selective markers for sensory and motor nerve terminals in rat lungs were used on lungs from control and vagotomized mice of two different strains, i.e., Swiss and C57-Bl6. NEB cells were visualized by antibodies against either the general neuroendocrine marker protein gene-product 9.5 (PGP9.5) or calcitonin gene-related peptide (CGRP). Thorough immunohistochemical examination of NEB cells showed that some of these NEB cells also exhibit calbindin D-28 k (CB) and vesicular acetylcholine transporter (VAChT) immunoreactivity (IR). Mouse pulmonary NEBs were found to receive intraepithelial nerve terminals of at least two different populations of myelinated vagal afferents: (1) Immunoreactive (ir) for vesicular glutamate transporters (VGLUTs) and CB; (2) expressing P2X(2) and P2X(3) ATP receptors. CGRP IR was seen in varicose vagal nerve fibers and in delicate non-vagal fibers, both in close proximity to NEBs. VAChT immunostaining showed very weak IR in the NEB-related intraepithelial vagal sensory nerve terminals. nNOS- or VIP-ir nerve terminals could be observed at the base of pulmonary NEBs. While a single NEB can be contacted by multiple nerve fiber populations, it was clear that none of the so far characterized nerve fiber populations contacts all pulmonary NEBs. The present study revealed that mouse lungs harbor several populations of nerve terminals that may selectively contact NEBs. Although at present the physiological significance of the innervation pattern of NEBs remains enigmatic, it is likely that NEBs are receptor-effector end-organs that may host complex and/or multiple functional properties in normal airways. The neurochemical information on the innervation of NEBs in mouse lungs gathered in the present study will be essential for the interpretation of upcoming functional data and for the study of transgenic mice