Abstract
Adenosine triphosphate (ATP) is a universal energy source synthesized by mitochondrial oxidative phosphorylation and cytosolic glycolysis and transported by the vesicular nucleotide transporter for storage in secretory vesicles. Extracellular ATP regulates physiological functions and homeostasis of the respiratory system and is associated with pathogenesis of respiratory diseases. Thus, modulation of ATP and purinergic signaling may be a novel therapeutic approach to pulmonary disease. ATP is released from alveolar epithelial cells, airway epithelial cells, airway smooth muscle cells, fibroblasts and endothelial cells in response to various chemical and mechanical stimuli. In addition to conductive pathways such as connexins and pannexins, vesicular exocytosis is involved in the mechanisms of ATP release from the cells. Imaging approaches enable us to visualize ATP release from not only cultured cells but also lung tissue ex vivo. Extracellular vesicles, exosomes and membrane-derived microvesicles, containing cytoplasmic proteins, mRNA and microRNA, represent important mediators of cell-to-cell communication and the intercellular microenvironment. However, it is not known whether extracellular vesicles contain ATP as an intercellular messenger. Future studies are necessary to elucidate the mechanisms of cellular ATP release and purinergic signaling in the respiratory system.
Highlights
It is widely recognized that adenosine triphosphate (ATP) acts as an extracellular messenger by activating purinergic receptors via autocrine and paracrine signaling [1]
Application of lipoxin A4 to airway epithelial cell lines derived from cystic fibrosis induces ATP release and subsequent activation of P2Y11 receptor, which leads to an increase in height of airway surface liquid layer [25]
Biophysics et al improved the luminescence imaging using an image intensifier with EM-CCD camera under a upright microscope and enabled simultaneous observation of bioluminescence of ATP and differential interference contrast (DIC) images of the cells and tissues using infrared (IR) optics [13,49,65,69]. Using this imaging system coupled with a cell-stretching apparatus, we visualized the extracellular ATP released from human airway smooth muscle (ASM) cells [13] and pulmonary microvascular endothelial cells in response to a single mechanical stretch in real time
Summary
It is widely recognized that adenosine triphosphate (ATP) acts as an extracellular messenger by activating purinergic receptors via autocrine and paracrine signaling [1]. ATP and its metabolite adenosine are important luminal autocrine and paracrine signals that regulate the hydration of airway epithelial cells [20,21]. Application of lipoxin A4 to airway epithelial cell lines derived from cystic fibrosis induces ATP release and subsequent activation of P2Y11 receptor, which leads to an increase in height of airway surface liquid layer [25]. Lipoxin A4 and ATP/purinergic signaling is expected as potentially a novel therapy for patients with cystic fibrosis lung disease [1]. Extracellular ATP and purinergic signaling are considered to be involved in various respiratory diseases including asthma, COPD, pulmonary fibrosis, lung injury and lung cancer [1,3,4,9,15,27,28].
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