Abstract
The lungs conceptually represent a sponge that is interposed in series in the bodies’ systemic circulation to take up oxygen and eliminate carbon dioxide. As such, it matches the huge surface areas of the alveolar epithelium to the pulmonary blood capillaries. The lung’s constant exposure to the exterior necessitates a competent immune system, as evidenced by the association of clinical immunodeficiencies with pulmonary infections. From the in utero to the postnatal and adult situation, there is an inherent vital need to manage alveolar fluid reabsorption, be it postnatally, or in case of hydrostatic or permeability edema. Whereas a wealth of literature exists on the physiological basis of fluid and solute reabsorption by ion channels and water pores, only sparse knowledge is available so far on pathological situations, such as in microbial infection, acute lung injury or acute respiratory distress syndrome, and in the pulmonary reimplantation response in transplanted lungs. The aim of this review is to discuss alveolar liquid clearance in a selection of lung injury models, thereby especially focusing on cytokines and mediators that modulate ion channels. Inflammation is characterized by complex and probably time-dependent co-signaling, interactions between the involved cell types, as well as by cell demise and barrier dysfunction, which may not uniquely determine a clinical picture. This review, therefore, aims to give integrative thoughts and wants to foster the unraveling of unmet needs in future research.
Highlights
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are both clinical syndromes with a high morbidity and mortality rate
The results show that Tumor necrosis factor (TNF) decreased the expression of the α, β, and γ-subunits of Epithelial sodium Transforming growth factor channel (ENaC) mRNA after 24-h treatment and reduced to 50% the amount of ENaC-α protein in these cells [135]
Consistent with the experimental results, high pulmonary edema fluid levels of IL-8 (>4,000 pg/ml) were associated with impaired alveolar fluid clearance (AFC) in patients with ALI. These results suggest a role for IL-8 in inhibiting β2adrenergic receptor (β2AR) agonist-stimulated alveolar epithelial fluid transport via a G-protein-coupled receptor kinase 2 (GRK2)/phosphoinositide 3-kinase (PI3K)-dependent mechanism [105]
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are both clinical syndromes with a high morbidity and mortality rate. As recently demonstrated by several groups, the interaction between cytokines and ion channels may play a critical role in this setting. The presented review does not cover all cytokines and ion channels, but rather focuses on a selection of mainly pre-clinical pathophysiological models and addresses clinical needs and difficulties to effectively translate pre-clinical data into the clinical field. The ultimate aim of this translational research should be to improve patient care and to reduce morbidity and mortality. This can be achieved by reducing long-term residual sequelae and time on the ventilator, which can improve long-term lung function and health status or health-related quality of life
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