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The purinergic events regulating the airways’ innate defenses are initiated by the release of purines from the epithelium, which occurs constitutively and is enhanced by chemical or mechanical stimulation. While the external triggers have been reviewed exhaustively, this chapter focuses on current knowledge of the receptors and signaling cascades mediating nucleotide release. The list of secreted...
In the respiratory system, extracellular nucleotides and nucleosides serve as signaling molecules for a wide spectrum of biological functions regulating airway defenses against infection and toxic material. Their concentrations are controlled by a complex network of cell surface enzymes named ectonucleotidases. This highly integrated metabolic network combines the activities of three dephosphorylating...
Extracellular nucleotides are key components of the signaling network regulating airway clearance. They are released by the epithelium into the airway surface liquid (ASL) to stimulate cilia beating activity, mucus secretion and airway hydration. Understanding the factors affecting their availability for purinoceptor activation is an important step toward the development of new therapies for obstructive...
The physiological relevance of the purinergic signaling network for airway defenses is emerging through cumulating reports of abnormal ATP and adenosine (ADO) levels in the airway secretions of patients with asthma, chronic pulmonary obstructive diseases, cystic fibrosis and idiopathic pulmonary fibrosis. The consequences for airway defenses range from abnormal clearance responses to the destruction...
A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept...
Airway epithelia are continuously damaged by airborne pollutants, pathogens and allergens, and they rely on intrinsic mechanisms to restore barrier integrity. Epithelial repair is a multi-step process including cell migration into the wounded area, proliferation, differentiation and matrix deposition. Each step requires the secretion of various molecules, including growth factors, integrins and matrix...
The immune and inflammatory responses initiated by the interaction of a pathogen with airway surfaces constitute vital mechanisms to eradicate an infection. Sentinel dendritic cells embedded in the mucosa migrate to the lymph nodes to induce immune responses, whereas epithelial cells release chemokines to recruit inflammatory cells engaged in the active destruction of the intruder. All immune and...
Over the past 20 years, the growing awareness that purinergic signaling events literally shape the immune and inflammatory responses to infection and allergic reactions warranted the development of animal models to assess their importance in vivo in acute lung injury and chronic airway diseases. The pioneer work conducted with the adenosine deaminase (ADA)-deficient mouse provided irrefutable evidence...
The current treatments offered to patients with chronic respiratory diseases are being re-evaluated based on the loss of potency during long-term treatments or because they only provide significant clinical benefits to a subset of the patient population. For instance, glucocorticoids are considered the most effective anti-inflammatory therapies for chronic inflammatory and immune diseases, such as...
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