Reactive Species Mediate Inhibition of Alveolar Type II Sodium Transport during Mycoplasma Infection

Hickman-Davis, Judy M.; McNicholas-Bevensee, Carmel M.; Davis, Ian C.; Ma, Heping; Davis, Glenda C.; Bosworth, Charles A.; Matalon, Sadis

doi:10.1164/rccm.200501-155oc

Cited by 57 publications

(57 citation statements)

References 68 publications

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“…Furthermore, infection with Mycoplasma pulmonis has been shown to suppress the amiloride-sensitive current that can be recorded from such cells, and this inhibitory response occurs with no change to the overall abundance of the ␣-, ␤-, and ␥-ENaC proteins. However, assays of surface expression showed that infection with M. pulmonis caused a fall in the surface abundance of ␥-ENaC that occurred with no effect on ␣-ENaC (21). Subsequent studies of H441 cells must therefore explore the effects of hormonal stimulation, SGK1/PI3K expression, and cell-cell contact on the surface expression of ␣-, ␤-, and ␥-ENaC.…”

Section: Discussionmentioning

confidence: 99%

The regulation of selective and nonselective Na⁺ conductances in H441 human airway epithelial cells

Brown

Gallacher²,

Olver³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionmentioning

confidence: 99%

The regulation of selective and nonselective Na⁺ conductances in H441 human airway epithelial cells

Brown

Gallacher²,

Olver³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…AFC Measurements-Alveolar fluid clearance was measured as previously described (7,23). In brief, mice were anesthetized and paralyzed by intraperitoneal injections of diazepam (10 mg/kg body weight; Hospira, Lake Forest, IL), ketamine (200 mg/kg; IVX Animal Health, St. Joseph, MO), and pancuronium bromide (0.04 mg; Gensia Pharmaceuticals, Irvine, CA).…”

Section: Methodsmentioning

confidence: 99%

“…However, the effects of Cl 2 inhalation on Na ϩ -dependent alveolar fluid clearance (AFC) in vivo as well as the mechanisms by which Cl 2 and HOCl damage ENaC have not been investigated. This is an important area of research as damage to ENaC has been associated with abnormal fluid transport in various forms of lung injury (7,(21)(22)(23)(24)(25).…”

mentioning

confidence: 99%

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines

Song¹,

Wei²,

Zhou³

et al. 2010

Journal of Biological Chemistry

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We investigated the mechanisms by which chlorine (Cl 2 ) and its reactive byproducts inhibit Na ؉ -dependent alveolar fluid clearance (AFC) in vivo and the activity of amiloridesensitive epithelial Na ؉ channels (ENaC) by measuring AFC in mice exposed to Cl 2 (0 -500 ppm for 30 min) and Na ؉ and amiloride-sensitive currents (I Na and I amil , respectively) across Xenopus oocytes expressing human ␣-, ␤-, and ␥-ENaC incubated with HOCl (1-2000 M). Both Cl 2 and HOCl-derived products decreased AFC in mice and whole cell and single channel I Na in a dose-dependent manner; these effects were counteracted by serine proteases. Mass spectrometry analysis of the oocyte recording medium identified organic chloramines formed by the interaction of HOCl with HEPES (used as an extracellular buffer). In addition, chloramines formed by the interaction of HOCl with taurine or glycine decreased I Na in a similar fashion. Preincubation of oocytes with serine proteases prevented the decrease of I Na by HOCl, whereas perfusion of oocytes with a synthetic 51-mer peptide corresponding to the putative furin and plasmin cleaving segment in the ␥-ENaC subunit restored the ability of HOCl to inhibit I Na . Finally, I Na of oocytes expressing wild type ␣-and ␥-ENaC and a mutant form of ␤ENaC (S520K), known to result in ENaC channels locked in the open position, were not altered by HOCl. We concluded that HOCl and its reactive intermediates (such as organic chloramines) inhibit ENaC by affecting channel gating, which could be relieved by proteases cleavage.The balance of fluid covering the respiratory and alveolar epithelia is determined in part by the ability of these cells to transport sodium (Na ϩ ) and chloride (Cl Ϫ ) ions in a vectorial fashion. Active Na ϩ reabsorption across lung epithelia requires the coordinated entry of Na ϩ ions through cation-and Na ϩ -selective amiloride-sensitive channels (ENaC) 5 located at the apical membranes, their extrusion across the basolateral membranes by the electrogenic Na ϩ -K ϩ -ATPase, and the passive movement of K ϩ ions through basolateral K ϩ channels. The entry of Na ϩ ions through apical pathways is thought to be the rate-limiting step in this process (1-3). To preserve neutrality, Cl Ϫ ions follow Na ϩ ions both through transcellular and paracellular pathways (4, 5). The coordinated movement of Na ϩ and Cl Ϫ ions creates an oncotic gradient favoring the absorption of alveolar fluid.Injury to either apical or basolateral pathways by partially reduced intermediates may lead to impairment of fluid reabsorption, which in turn may result in pulmonary edema, hypoxemia, and eventually death from respiratory failure (6 -9). One such specie is hypochlorous acid (HOCl) 6 , which may be generated either endogenously or exogenously. Millimolar concentrations of HOCl may be generated by activated neutrophils and eosinophils by the catalytic actions of neutrophil-and eosinophil-derived myeloperoxidases on chloride (Cl Ϫ ) and hydrogen peroxide (H 2 O 2 ) in close proximity of the apical and basolatera...

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“…Patch-clamp recording was measured as previously reported (38). Immediately before each experiment, a coverslip bearing primary ATII cells was removed from the culture plate into a recording chamber, which was mounted on the stage of an inverted fluorescent microscope (Leica DM IRB).…”

Section: Electrophysiologymentioning

confidence: 99%

Resolvin D1 Stimulates Alveolar Fluid Clearance through Alveolar Epithelial Sodium Channel, Na,K-ATPase via ALX/cAMP/PI3K Pathway in Lipopolysaccharide-Induced Acute Lung Injury

Wang

Zheng

Cheng

et al. 2014

The Journal of Immunology

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Resolvin D1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) (RvD1), generated from ω-3 fatty docosahexaenoic acids, is believed to exert anti-inflammatory properties including inhibition of neutrophil activation and regulating inflammatory cytokines. In this study, we sought to investigate the effect of RvD1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. In vivo, RvD1 was injected i.v. (5 μg/kg) 8 h after LPS (20 mg/kg) administration, which markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema. In addition, rat lung tissue protein was isolated after intervention and we found RvD1 improved epithelial sodium channel (ENaC) α, γ, Na,K-adenosine triphosphatase (ATPase) α1, β1 subunit protein expression and Na,K-ATPase activity. In primary rat alveolar type II epithelial cells stimulated with LPS, RvD1 not only upregulated ENaC α, γ and Na,K-ATPase α1 subunits protein expression, but also increased Na+ currents and Na,K-ATPase activity. Finally, protein kinase A and cGMP were not responsible for RvD1’s function because a protein kinase A inhibitor (H89) and cGMP inhibitor (Rp-cGMP) did not reduce RvD1’s effects. However, the RvD1 receptor (formyl-peptide receptor type 2 [FPR2], also called ALX [the lipoxin A4 receptor]) inhibitor (BOC-2), cAMP inhibitor (Rp-cAMP), and PI3K inhibitor (LY294002) not only blocked RvD1’s effects on the expression of ENaC α in vitro, but also inhibited the AFC in vivo. In summary, RvD1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/cAMP/PI3K signaling pathway.

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Reactive Species Mediate Inhibition of Alveolar Type II Sodium Transport during Mycoplasma Infection

Cited by 57 publications

References 68 publications

The regulation of selective and nonselective Na⁺ conductances in H441 human airway epithelial cells

The regulation of selective and nonselective Na⁺ conductances in H441 human airway epithelial cells

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines

Resolvin D1 Stimulates Alveolar Fluid Clearance through Alveolar Epithelial Sodium Channel, Na,K-ATPase via ALX/cAMP/PI3K Pathway in Lipopolysaccharide-Induced Acute Lung Injury

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Reactive Species Mediate Inhibition of Alveolar Type II Sodium Transport during Mycoplasma Infection

Cited by 57 publications

References 68 publications

The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells

The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines

Resolvin D1 Stimulates Alveolar Fluid Clearance through Alveolar Epithelial Sodium Channel, Na,K-ATPase via ALX/cAMP/PI3K Pathway in Lipopolysaccharide-Induced Acute Lung Injury

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The regulation of selective and nonselective Na⁺ conductances in H441 human airway epithelial cells

The regulation of selective and nonselective Na⁺ conductances in H441 human airway epithelial cells