Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung

2007 ◽  
Vol 292 (2) ◽  
pp. F586-F592 ◽  
Author(s):  
Lúcia Andrade ◽  
Adílson C. Rodrigues ◽  
Talita R. C. Sanches ◽  
Rodrigo B. Souza ◽  
Antonio Carlos Seguro
Keyword(s):  
Pulmonary Edema ◽  
Sodium Transport ◽  
Public Health Problem ◽  
Alveolar Epithelial Cells ◽  
Lung Edema ◽  
Alveolar Epithelial ◽  
Sodium Transporters ◽  
Aquaporin 2 ◽  
Sodium Hydrogen Exchanger ◽  
Urinary Concentrating Ability

Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.

scholarly journals Amiloride-Sensitive Sodium Channels and Pulmonary Edema

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Mike Althaus ◽  
Wolfgang G. Clauss ◽  
Martin Fronius
Keyword(s):  
Pulmonary Edema ◽  
Sodium Channels ◽  
Sodium Transport ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Alveolar Fluid Clearance ◽  
Fluid Filtration ◽  
Alveolar Epithelial ◽  
Transepithelial Sodium Transport ◽  
Alveolar Capillary

The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed.

scholarly journals Overexpression of Sphingosine Kinase-1 and Sphingosine-1-Phosphate Receptor-3 in Severe Plasmodium falciparum Malaria with Pulmonary Edema

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Parnpen Viriyavejakul ◽  
Chuchard Punsawad
Keyword(s):  
Plasmodium Falciparum ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Sphingosine Kinase ◽  
Alveolar Epithelial Cells ◽  
Sphingosine Kinase 1 ◽  
Expression Levels ◽  
Alveolar Epithelial ◽  
Sphingosine 1 Phosphate

Pulmonary edema (PE) is a major cause of pulmonary manifestations of severe Plasmodium falciparum malaria and is usually associated with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The sphingosine kinase-1 (SphK-1)/sphingosine-1-phosphate receptor-3 (S1PR-3) pathway has recently been reported to affect the pathogenesis of lung injury, but the expression of these proteins in the lungs of severe P. falciparum malaria patients has not been investigated. The cellular expression of SphK-1 and S1PR-3 in lung tissues from autopsied patients with P. falciparum malaria was investigated using immunohistochemistry (IHC). Lung tissues from patients who died of severe P. falciparum malaria were classified into two groups based on histopathological findings: those with PE (18 patients) and those without PE (non-PE, 19 patients). Ten samples of normal lung tissues were used as the control group. The protein expression levels of SphK-1 and S1PR-3 were significantly upregulated in endothelial cells (ECs), alveolar epithelial cells, and alveolar macrophages (AMs) in the lungs of severe P. falciparum malaria patients with PE compared to those in the non-PE and control groups (all p<0.001). In addition, the SphK-1 and S1PR-3 expression levels were significantly positively correlated in pulmonary ECs (rs=0.922, p<0.001), alveolar epithelial cells (rs=0.995, p<0.001), and AMs (rs=0.969, p<0.001). In conclusion, both the SphK-1 and S1PR-3 proteins were overexpressed in the lung tissues of severe P. falciparum malaria patients with PE, suggesting that SphK-1 and S1PR-3 mediate the pathogenesis of PE in severe malaria. Targeting the regulation of SphK-1 and/or S1PR-3 may be an approach to treat pulmonary complications in severe P. falciparum patients.

Tight monolayers of rat alveolar epithelial cells: bioelectric properties and active sodium transport

1989 ◽  
Vol 256 (3) ◽  
pp. C688-C693 ◽  
Author(s):  
J. M. Cheek ◽  
K. J. Kim ◽  
E. D. Crandall
Keyword(s):  
Epithelial Cells ◽  
Sodium Transport ◽  
Short Circuit ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Active Sodium ◽  
Alveolar Epithelial ◽  
Active Sodium Transport ◽  
Complex Anatomy

Because the pulmonary alveolar epithelium separates air spaces from a fluid-filled compartment, it is expected that this barrier would be highly resistant to the flow of solutes and water. Investigation of alveolar epithelial resistance has been limited due to the complex anatomy of adult mammalian lung. Previous efforts to study isolated alveolar epithelium cultured on porous substrata yielded leaky monolayers. In this study, alveolar epithelial cells isolated from rat lungs and grown on tissue culture-treated Nucleopore filters resulted in tight monolayers with transepithelial resistance greater than 2,000 omega.cm2. Changes in bioelectric properties of these alveolar epithelial monolayers in response to ouabain, amiloride, and terbutaline are consistent with active sodium transport across a polarized barrier. 22Na flux measurements under short-circuit conditions directly confirm net transepithelial absorption of sodium by alveolar epithelial cells in the apical to basolateral direction, comparable to the observed short-circuit current (4.37 microA/cm2). The transport properties of these tight monolayers may be representative of the characteristics of the mammalian alveolar epithelial barrier in vivo.

Mechanical stretching of alveolar epithelial cells increases Na+-K+-ATPase activity

1999 ◽  
Vol 87 (2) ◽  
pp. 715-721 ◽  
Author(s):  
Christopher M. Waters ◽  
Karen M. Ridge ◽  
G. Sunio ◽  
K. Venetsanou ◽  
Jacob Iasha Sznajder
Keyword(s):  
Epithelial Cells ◽  
Atpase Activity ◽  
Basolateral Membrane ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Cyclic Stretch ◽  
Lung Edema ◽  
Alveolar Epithelial ◽  
A Cell

Alveolar epithelial cells effect edema clearance by transporting Na+ and liquid out of the air spaces. Active Na+ transport by the basolaterally located Na+-K+-ATPase is an important contributor to lung edema clearance. Because alveoli undergo cyclic stretch in vivo, we investigated the role of cyclic stretch in the regulation of Na+-K+-ATPase activity in alveolar epithelial cells. Using the Flexercell Strain Unit, we exposed a cell line of murine lung epithelial cells (MLE-12) to cyclic stretch (30 cycles/min). After 15 min of stretch (10% mean strain), there was no change in Na+-K+-ATPase activity, as assessed by86Rb+uptake. By 30 min and after 60 min, Na+-K+-ATPase activity was significantly increased. When cells were treated with amiloride to block amiloride-sensitive Na+ entry into cells or when cells were treated with gadolinium to block stretch-activated, nonselective cation channels, there was no stimulation of Na+-K+-ATPase activity by cyclic stretch. Conversely, cells exposed to Nystatin, which increases Na+ entry into cells, demonstrated increased Na+-K+-ATPase activity. The changes in Na+-K+-ATPase activity were paralleled by increased Na+-K+-ATPase protein in the basolateral membrane of MLE-12 cells. Thus, in MLE-12 cells, short-term cyclic stretch stimulates Na+-K+-ATPase activity, most likely by increasing intracellular Na+ and by recruitment of Na+-K+-ATPase subunits from intracellular pools to the basolateral membrane.

scholarly journals The Fas/FasL pathway impairs the alveolar fluid clearance in mouse lungs

2013 ◽  
Vol 305 (5) ◽  
pp. L377-L388 ◽  
Author(s):  
Raquel Herrero ◽  
Mishie Tanino ◽  
Lincoln S. Smith ◽  
Osamu Kajikawa ◽  
Venus A. Wong ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Fas Ligand ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Critical Event ◽  
Lung Edema ◽  
Adrenergic Stimulation ◽  
Epithelial Damage ◽  
Alveolar Epithelial ◽  
Mouse Lungs

Alveolar epithelial damage is a critical event that leads to protein-rich edema in acute lung injury (ALI), but the mechanisms leading to epithelial damage are not completely understood. Cell death by necrosis and apoptosis occurs in alveolar epithelial cells in the lungs of patients with ALI. Fas activation induces apoptosis of alveolar epithelial cells, but its role in the formation of lung edema is unclear. The main goal of this study was to determine whether activation of the Fas/Fas ligand pathway in the lungs could alter the function of the lung epithelium, and the mechanisms involved. The results show that Fas activation alters the alveolar barrier integrity and impairs the ability of the lung alveolar epithelium to reabsorb fluid from the air spaces. This result was dependent on the presence of a normal Fas receptor and was not affected by inflammation induced by Fas activation. Alteration of the fluid transport properties of the alveolar epithelium was partially restored by β-adrenergic stimulation. Fas activation also caused apoptosis of alveolar endothelial cells, but this effect was less pronounced than the effect on the alveolar epithelium. Thus, activation of the Fas pathway impairs alveolar epithelial function in mouse lungs by mechanisms involving caspase-dependent apoptosis, suggesting that targeting apoptotic pathways could reduce the formation of lung edema in ALI.

Downregulation of ENaC activity and expression by TNF-α in alveolar epithelial cells

2004 ◽  
Vol 286 (2) ◽  
pp. L301-L311 ◽  
Author(s):  
André Dagenais ◽  
Rosalie Fréchette ◽  
Yuko Yamagata ◽  
Toshiyuki Yamagata ◽  
Jean-François Carmel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Proinflammatory Cytokine ◽  
Alveolar Epithelial Cells ◽  
Sodium Absorption ◽  
Lung Edema ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Lung Liquid ◽  
Factor Α

Sodium absorption by an amiloride-sensitive channel is the main driving force of lung liquid clearance at birth and lung edema clearance in adulthood. In this study, we tested whether tumor necrosis factor-α (TNF-α), a proinflammatory cytokine involved in several lung pathologies, could modulate sodium absorption in cultured alveolar epithelial cells. We found that TNF-α decreased the expression of the α-, β-, and γ-subunits of epithelial sodium channel (ENaC) mRNA to 36, 43, and 16% of the controls after 24-h treatment and reduced to 50% the amount of α-ENaC protein in these cells. There was no impact, however, on α1and β1Na+-K+-ATPase mRNA expression. Amiloride-sensitive current and ouabain-sensitive Rb+uptake were reduced, respectively, to 28 and 39% of the controls. A strong correlation was found at different TNF-α concentrations between the decrease of amiloride-sensitive current and α-ENaC mRNA expression. All these data show that TNF-α, a proinflammatory cytokine present during lung infection, has a profound influence on the capacity of alveolar epithelial cells to transport sodium.

scholarly journals Adenosine A2B receptor activation stimulates alveolar fluid clearance through alveolar epithelial sodium channel via cAMP pathway in endotoxin-induced lung injury

2020 ◽  
Vol 318 (4) ◽  
pp. L787-L800
Author(s):  
Mengnan Wang ◽  
Xiaoxia Guo ◽  
Huiying Zhao ◽  
Jie Lv ◽  
Huixia Wang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Sodium Channel ◽  
Pulmonary Edema ◽  
Epithelial Sodium Channel ◽  
Receptor Activation ◽  
Alveolar Epithelial Cells ◽  
Alveolar Fluid Clearance ◽  
Alveolar Epithelial ◽  
Camp Pathway

Clinical studies have established that the capacity of removing excess fluid from alveoli is impaired in most patients with acute respiratory distress syndrome. Impaired alveolar fluid clearance (AFC) correlates with poor outcomes. Adenosine A2B receptor (A2BAR) has the lowest affinity with adenosine among four adenosine receptors. It is documented that A2BAR can activate adenylyl cyclase (AC) resulting in elevated cAMP. Based on the understanding that cAMP is a key regulator of epithelial sodium channel (ENaC), which is the limited step in sodium transport, we hypothesized that A2BAR signaling may affect AFC in acute lung injury (ALI) through regulating ENaC via cAMP, thus attenuating pulmonary edema. To address this, we utilized pharmacological approaches to determine the role of A2BAR in AFC in rats with endotoxin-induced lung injury and further focused on the mechanisms in vitro. We observed elevated pulmonary A2BAR level in rats with ALI and the similar upregulation in alveolar epithelial cells exposed to LPS. A2BAR stimulation significantly attenuated pulmonary edema during ALI, an effect that was associated with enhanced AFC and increased ENaC expression. The regulatory effects of A2BAR on ENaC-α expression were further verified in cultured alveolar epithelial type II (ATII) cells. More importantly, activation of A2BAR dramatically increased amiloride-sensitive Na+ currents in ATII cells. Moreover, we observed that A2BAR activation stimulated cAMP accumulation, whereas the cAMP inhibitor abolished the regulatory effect of A2BAR on ENaC-α expression, suggesting that A2BAR activation regulates ENaC-α expression via cAMP-dependent mechanism. Together, these findings suggest that signaling through alveolar epithelial A2BAR promotes alveolar fluid balance during endotoxin-induced ALI by regulating ENaC via cAMP pathway, raising the hopes for treatment of pulmonary edema due to ALI.

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