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Lysosomal Ion Channels and Human Diseases
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Peng Huang, Mengnan Xu, Yi Wu, Xian-Ping Dong
The P2X4 receptor (encoded by the P2RX4 gene) belongs to the family of purinoceptors that opens in response to ATP binding at the extracellular side (Khakh and North, 2012). It is a trimeric 2-TM channel permeable to both Na+ and Ca2+ when activated by ATP (Figure 18.5). P2X4 is highly expressed in the PM of various tissues and involved in many cellular processes. Recent studies suggest that P2X4 receptors are stored in the lysosomal membrane and brought to the cell surface or to phagosomes in response to a variety of stimuli (Qureshi et al., 2007). Lysosomal P2X4 is activated by luminal ATP in a pH-dependent manner, i.e. it is minimally activated at acidic luminal pH, whereas lysosome alkalization dramatically increases its activity. Physiologically, P2X4 functions as a lysosomal Ca2+ channel which activation facilitates homotypic lysosome fusion using a CaM-dependent mechanism (Cao et al., 2015a). P2X4 is also expressed in lysosome-related vesicles such as Lamellar Bodies, large secretory lysosomes that store lung surfactant in alveolar type II epithelial cells and is inserted into the PM following lysosomal exocytosis. New evidence suggests that the activation of vesicular P2X4 receptors facilitates the secretion of pulmonary surfactant in pulmonary alveoli (Fois et al., 2018; Miklavc et al., 2011; Thompson et al., 2013).
Drowning
Published in Burkhard Madea, Asphyxiation, Suffocation,and Neck Pressure Deaths, 2020
Once they reach the breath-hold breaking point, the victims breathe, causing liquid to enter the airways and eventually be swallowed. Stimulation of the laryngeal mucosa by the liquid can lead to reflex protective laryngospasm to prevent foreign materials reaching the lower airways [103]. During laryngospasm, respiratory movements against the closed glottis may cause mechanical damage to the pulmonary alveoli. A certain agreement exists over the transient nature of laryngospasm. As arterial oxygen tension drops and hypoxia ensues in laryngeal muscles, laryngospasm will abate, followed by involuntary gasping and penetration of liquid into the airways [11].
The Chemical Environment
Published in Vilma R. Hunt, Kathleen Lucas-Wallace, Jeanne M. Manson, Work and the Health of Women, 2020
Vilma R. Hunt, Kathleen Lucas-Wallace, Jeanne M. Manson
As gestation progresses, the placental membrane increases in surface area and decreases in thickness. At term, it is estimated that the membrane’s surface area is about one fifth that of the pulmonary alveoli and is three times as thick.
The blood-gas barrier in COVID-19: an overview of the effects of SARS-CoV-2 infection on the alveolar epithelial and endothelial cells of the lung
Published in Tissue Barriers, 2021
Consisting of tightly connected ‘alveolar epithelial cells’ (AECs), capillary ‘endothelial cells’ (ECs) and the ‘extracellular matrix’ (ECM) in between, the ‘blood-gas barrier’ (BGB) or ‘alveolar-capillary barrier’ (ACB) is a highly specialized wall spanning throughout the pulmonary alveoli, separating the inhaled air from the internal environment of the body. Damage to this extremely delicate wall1, which is only 0.2 to 0.3 μm thick2, might occur as a result of the inflammation caused by lower respiratory tract infections such as ‘coronavirus disease 2019ʹ (COVID-19)3. An acute inflammatory process, mediated chiefly by macrophage-derived cytokines like ‘interleukin-1ʹ (IL-1), IL-6 and ‘tumor necrosis factor alpha’ (TNF-α), can adversely affect the components of the BGB (Figure 1), and result in ‘acute respiratory distress syndrome’ (ARDS); a life-threatening condition with a relatively high mortality due to impaired gas exchange across the BGB1.
Could Vitamin C Protect Against Mercuric Chloride Induced Lung Toxicity In The Offspring Rat: A Histological And Immunohistochemical Study
Published in Ultrastructural Pathology, 2021
Omnia I. Ismail, Manal M.S. El-Meligy
Examination of Toluidine blue-stained semithin sections in the control group showed the alveoli appeared inflated well. The interalveolar septa revealed the type I pneumocyte, which had flat nuclei as well as the type II pneumocyte had cuboidal nuclei (Figure 3a). On the other hand, in the HgCl2-treated group the pulmonary alveoli were partially collapsed. Exfoliation of the alveolar lining was observed. The interalveolar septa with the type I pneumocyte and type II pneumocyte were degenerated. The alveolar lumen was filled with RBCs (Figure 3b). Remarkable partial improvement of the lung structure was detected in the HgCl2 + vitamin C-treated group. Some alveoli became well inflated; the others were still collapsed. In addition, the lumens of some alveoli were still filled with RBCs. Thin interalveolar septa were detected but the others were still appeared thick. Moreover, the type I pneumocyte and type II pneumocyte (PII) appeared more or less normal (Figure 3c).
The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case
Published in International Journal of Radiation Biology, 2021
Gustavo Viani Arruda, Raissa Renata dos Santos Weber, Alexandre Colello Bruno, Juliana Fernandes Pavoni
Pneumonia is an inflammatory immune response to infection. The pulmonary alveoli become inflamed, secreted fluid increases, and this compromises pulmonary function (Chen and Li 2020). In COVID-19, the immune cells are stimulated by the viruses to synthesize cytokines and chemokines, producing an immune response. This leads to pneumonia (Chen and Li 2020). There are currently limited clinical options for treating COVID-19 patients with pneumonia (Cascella et al. 2020). Therefore, some authors have suggested that radiotherapy (RT), with a total dose to the whole thorax ranging between 0.35 and 1.5 Gy, could be effective in reducing the inflammatory response. Moreover, a moderate dose will at the same time not appreciably increase the risk of radiation-induced cancer (RIC) for the patients being treated (Rödel et al. 2012; Yang et al. 2014; Dhawan et al. 2020; Kirkby and Mackenzie 2020; Kirsch et al. 2020; Salomaa, Cardis, et al. 2020).