The LRRC8A Mediated "Swell Activated" Chloride Conductance Is Dispensable for Vacuolar Homeostasis in Neutrophils.

Abstract:

:The dialysis of human and mouse neutrophils in patch clamp experiments in the conventional whole-cell mode induces the emergence of a chloride (Cl-) current that appeared to be primarily regulated by cytoplasmic ionic strength. The characteristics of this current resembled that of the classical, and ubiquitous volume-sensitive outwardly rectifying Cl- current: strong outward rectification, selectivity sequence of the Eisenman1 type, insensitivity to external pH and strong inhibition by tamoxifen, DCPIB and WW781. We show that this current is essentially supported by the leucine rich repeat containing 8 A (LRRC8A); the naturally occurring LRRC8A truncation mutant in ebo/ebo mice drastically reduced Cl- conductance in neutrophils. Remarkably, the residual component presents a distinct pharmacology, but appears equally potentiated by reduced ionic strength. We have investigated the role of the LRRC8A-supported current in the ionic homeostasis of the phagosomal compartment. The vacuolar pH, measured using SNARF-1 labeled Candida albicans, normally rises because of NADPH oxidase activity, and this elevation is blocked by certain Cl- channel inhibitors. However, the pH rise remains intact in neutrophils from the ebo/ebo mice which also demonstrate preserved phagocytic and respiratory burst capacities and normal-sized vacuoles. Thus, the LRRC8A-dependent conductance of neutrophils largely accounts for their "swell activated" Cl- current, but is not required for homeostasis of the phagosomal killing compartment.

journal_name

Front Pharmacol

authors

Behe P,Foote JR,Levine AP,Platt CD,Chou J,Benavides F,Geha RS,Segal AW

doi

10.3389/fphar.2017.00262

subject

Has Abstract

pub_date

2017-05-12 00:00:00

pages

262

issn

1663-9812

journal_volume

8

pub_type

杂志文章
  • Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration.

    abstract::Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H (CFH) gene; ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.591908

    authors: Stravalaci M,Davi F,Parente R,Gobbi M,Bottazzi B,Mantovani A,Day AJ,Clark SJ,Romano MR,Inforzato A

    更新日期:2020-11-26 00:00:00

  • Metabolomics Reveals the Efficacy of Caspase Inhibition for Saikosaponin D-Induced Hepatotoxicity.

    abstract::Saikosaponin d (SSd) is a major hepatoprotective component of saikosaponins derived from Radix Bupleuri, which was also linked to hepatotoxicity. Previous studies have demonstrated that caspases play a key role in SSd-induced liver cell death. Our in vitro and in vivo studies also showed that treatment with caspase in...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00732

    authors: Zhang QQ,Huang WQ,Gao YQ,Han ZD,Zhang W,Zhang ZJ,Xu FG

    更新日期:2018-07-06 00:00:00

  • Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels.

    abstract:Background:Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00691

    authors: Ortner M,Stange M,Schneider H,Schroeder C,Buerger K,Müller C,Dorn B,Goldhardt O,Diehl-Schmid J,Förstl H,Steimer W,Grimmer T

    更新日期:2020-05-21 00:00:00

  • Effect of Cognitive Style on Learning and Retrieval of Navigational Environments.

    abstract::Field independence (FI) has been found to correlate with a wide range of cognitive processes requiring cognitive restructuring. Cognitive restructuring, that is going beyond the information given by the setting, is pivotal in creating stable mental representations of the environment, the so-called "cognitive maps," an...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00496

    authors: Boccia M,Vecchione F,Piccardi L,Guariglia C

    更新日期:2017-07-25 00:00:00

  • Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.

    abstract::The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.00550

    authors: Brewer KR,Kuenze G,Vanoye CG,George AL Jr,Meiler J,Sanders CR

    更新日期:2020-05-04 00:00:00

  • Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology.

    abstract::Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00016

    authors: Yuan NN,Cai CZ,Wu MY,Zhu Q,Su H,Li M,Ren J,Tan JQ,Lu JH

    更新日期:2019-01-28 00:00:00

  • Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells.

    abstract::Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.01176

    authors: Chen Y,Liu X,Wang H,Liu S,Hu N,Li X

    更新日期:2019-10-11 00:00:00

  • Immunosuppressive Activity of Artemisia argyi Extract and Isolated Compounds.

    abstract::The need for novel drugs for the treatment of autoimmune diseases is high, since available pharmaceuticals often have substantial side effects and limited efficacy. Natural products are a good starting point in the development of immunosuppressive leads. Since enhanced T cell proliferation is a common feature of autoi...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00402

    authors: Zimmermann-Klemd AM,Reinhardt JK,Morath A,Schamel WW,Steinberger P,Leitner J,Huber R,Hamburger M,Gründemann C

    更新日期:2020-04-08 00:00:00

  • Dendrobium officinale Polysaccharide Protected CCl4-Induced Liver Fibrosis Through Intestinal Homeostasis and the LPS-TLR4-NF-κB Signaling Pathway.

    abstract::We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl4-induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00240

    authors: Wang K,Yang X,Wu Z,Wang H,Li Q,Mei H,You R,Zhang Y

    更新日期:2020-03-12 00:00:00

  • Localized Delivery of Cl-Amidine From Electrospun Polydioxanone Templates to Regulate Acute Neutrophil NETosis: A Preliminary Evaluation of the PAD4 Inhibitor for Tissue Engineering.

    abstract::Upon interaction, neutrophils can potentially release neutrophil extracellular traps (NETs) on the surface of an implanted electrospun template, which may be a significant preconditioning event for implantable biomaterials of yet unknown consequences. In this study, we investigated the potential of polydioxanone templ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00289

    authors: Fetz AE,Neeli I,Buddington KK,Read RW,Smeltzer MP,Radic MZ,Bowlin GL

    更新日期:2018-03-28 00:00:00

  • The role of CaMKII regulation of phospholamban activity in heart disease.

    abstract::Phospholamban (PLN) is a phosphoprotein in cardiac sarcoplasmic reticulum (SR) that is a reversible regulator of the Ca(2) (+)-ATPase (SERCA2a) activity and cardiac contractility. Dephosphorylated PLN inhibits SERCA2a and PLN phosphorylation, at either Ser(16) by PKA or Thr(17) by Ca(2) (+)-calmodulin-dependent protei...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2014.00005

    authors: Mattiazzi A,Kranias EG

    更新日期:2014-01-27 00:00:00

  • Toxicity and Pharmacogenomic Biomarkers in Breast Cancer Chemotherapy.

    abstract::Breast cancer (BC) is one of the most prevalent types of cancer worldwide with high morbidity and mortality rates. Treatment modalities include systemic therapy, in which chemotherapy is a major component in many cases. Several chemotherapeutic agents are used in combinations or as single agents with many adverse even...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.00445

    authors: Al-Mahayri ZN,Patrinos GP,Ali BR

    更新日期:2020-04-15 00:00:00

  • Monocytes, Macrophages, and Metabolic Disease in Atherosclerosis.

    abstract::Atherosclerotic cardiovascular disease (CVD) is a lipid-driven chronic inflammatory disease, in which macrophages are responsible for taking up these lipids and driving disease progression. Over the years, we and others have uncovered key pathways that regulate macrophage number/function and identified how metabolic d...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2019.00666

    authors: Flynn MC,Pernes G,Lee MKS,Nagareddy PR,Murphy AJ

    更新日期:2019-06-13 00:00:00

  • Recombinant Human Endostatin Suppresses Mouse Osteoclast Formation by Inhibiting the NF-κB and MAPKs Signaling Pathways.

    abstract::Rheumatoid arthritis is an autoimmune disease characterized by synovial hyperplasia and progressive joint destruction. As reported previously, recombinant human endostatin (rhEndostatin) is associated with inhibition of joint bone destruction present in rat adjuvant-induced arthritis; however, the effect of rhEndostat...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00145

    authors: Chen N,Gao RF,Yuan FL,Zhao MD

    更新日期:2016-06-01 00:00:00

  • In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber.

    abstract::Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in viv...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.01287

    authors: Wu D,Wang Z,Lin M,Shang Y,Wang F,Zhou J,Wang F,Zhang X,Luo X,Huang W

    更新日期:2019-11-08 00:00:00

  • Proanthocyanidin Polymer-Rich Fraction of Stryphnodendron adstringens Promotes in Vitro and in Vivo Cancer Cell Death via Oxidative Stress.

    abstract::Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00694

    authors: Kaplum V,Ramos AC,Consolaro MEL,Fernandez MA,Ueda-Nakamura T,Dias-Filho BP,Silva SO,de Mello JCP,Nakamura CV

    更新日期:2018-07-03 00:00:00

  • Promises and pitfalls of a Pannexin1 transgenic mouse line.

    abstract::Gene targeting strategies have become a powerful technology for elucidating mammalian gene function. The recently generated knockout (KO)-first strategy produces a KO at the RNA processing level and also allows for the generation of conditional KO alleles by combining FLP/FRT and Cre/loxP systems, thereby providing hi...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2013.00061

    authors: Hanstein R,Negoro H,Patel NK,Charollais A,Meda P,Spray DC,Suadicani SO,Scemes E

    更新日期:2013-05-09 00:00:00

  • Antidepressant and Anti-Neuroinflammatory Effects of Bangpungtongsung-San.

    abstract::Bangpungtongsung-san (BTS) is a traditional Korean medicine consisting of 18 herbs, some which have antidepressant effects. Here, we used an animal model of reserpine-induced depression and lipopolysaccharide (LPS)-stimulated BV2 microglia to assess the antidepressant and anti-neuroinflammatory effects of BTS. Aside f...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00958

    authors: Park BK,Kim NS,Kim YR,Yang C,Jung IC,Jang IS,Seo CS,Choi JJ,Lee MY

    更新日期:2020-07-10 00:00:00

  • Nrf2 as a Potential Mediator of Cardiovascular Risk in Metabolic Diseases.

    abstract::Free radicals act as secondary messengers, modulating a number of important biological processes, including gene expression, ion mobilization in transport systems, protein interactions and enzymatic functions, cell growth, cell cycle, redox homeostasis, among others. In the cardiovascular system, the physiological gen...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2019.00382

    authors: da Costa RM,Rodrigues D,Pereira CA,Silva JF,Alves JV,Lobato NS,Tostes RC

    更新日期:2019-04-12 00:00:00

  • Convenience versus Biological Significance: Are PMA-Differentiated THP-1 Cells a Reliable Substitute for Blood-Derived Macrophages When Studying in Vitro Polarization?

    abstract::Human peripheral-blood monocytes are used as an established in vitro system for generating macrophages. For several reasons, monocytic cell lines such as THP-1 have been considered as a possible alternative. In view of their distinct developmental origins and phenotypic attributes, we set out to assess the extent to w...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00071

    authors: Tedesco S,De Majo F,Kim J,Trenti A,Trevisi L,Fadini GP,Bolego C,Zandstra PW,Cignarella A,Vitiello L

    更新日期:2018-02-22 00:00:00

  • Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell.

    abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD). Ethanol induces adaptations in glutamatergic synapses onto nu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00533

    authors: Mangieri RA,Maier EY,Buske TR,Lasek AW,Morrisett RA

    更新日期:2017-08-15 00:00:00

  • Retraction: Baicalin induced dendritic cell apoptosis in vitro.

    abstract::[This retracts the article on p. 15 in vol. 2, PMID: 21687510.]. ...

    journal_title:Frontiers in pharmacology

    pub_type: 撤回出版物

    doi:10.3389/fphar.2014.00283

    authors: Frontiers in Pharmacology Editorial Office.

    更新日期:2014-12-17 00:00:00

  • Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking.

    abstract::Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal contr...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00498

    authors: Yong T,Chen S,Xie Y,Shuai O,Li X,Chen D,Su J,Jiao C,Liang Y

    更新日期:2018-05-15 00:00:00

  • Factors Associated With Response and Resistance to Cognitive Remediation in Schizophrenia: A Critical Review.

    abstract::Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systema...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2018.01542

    authors: Barlati S,Deste G,Galluzzo A,Perin AP,Valsecchi P,Turrina C,Vita A

    更新日期:2019-01-10 00:00:00

  • ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts.

    abstract::Background: Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this st...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.615505

    authors: Yang X,Xiao Y,Zhong C,Shu F,Xiao S,Zheng Y,Xia Z

    更新日期:2021-01-14 00:00:00

  • Glucocorticoid-Induced Leucine Zipper: A Novel Anti-inflammatory Molecule.

    abstract::Glucocorticoids (GCs) are the most commonly used drugs for treatment of autoimmune and inflammatory diseases. Their efficacy is due to their ability to bind cytoplasmic receptors (glucocorticoid receptors, GR) and other cytoplasmic proteins, thus regulating gene expression. Although GCs are potent life-saving drugs, t...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2019.00308

    authors: Bereshchenko O,Migliorati G,Bruscoli S,Riccardi C

    更新日期:2019-03-27 00:00:00

  • Physiological implications of NTBI uptake by T lymphocytes.

    abstract::In iron overload disorders a significant fraction of the total iron circulates in the plasma as low molecular weight complexes not bound to transferrin, known as non-transferrin-bound iron (NTBI). By catalyzing the formation of free radicals, NTBI accumulation results in oxidative stress and cellular damage, being a m...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2014.00024

    authors: Pinto JP,Arezes J,Dias V,Oliveira S,Vieira I,Costa M,Vos M,Carlsson A,Rikers Y,Rangel M,Porto G

    更新日期:2014-02-26 00:00:00

  • Practical Barriers to Medication Adherence: What Do Current Self- or Observer-Reported Instruments Assess?

    abstract:Introduction:Practical adherence barriers (e.g., medication frequency) are generally more amenable to intervention than perceptual barriers (e.g., beliefs). Measures which assess adherence barriers exist, however these tend to measure a mix of factors. There is a need to identify what practical barriers are captured by...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.00572

    authors: Chan AHY,Cooper V,Lycett H,Horne R

    更新日期:2020-05-13 00:00:00

  • Pelvic Ultrasound in Diagnosing and Evaluating the Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls With Idiopathic Central Precocious Puberty.

    abstract::Background and Objective: Idiopathic central precocious puberty (ICPP) is characterized by early pubertal changes, the acceleration of growth velocity, and rapid bone maturation that often results in reduced adult height. Gonadotrophin-releasing hormone agonist (GnRHa) is currently considered to be an effective therap...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00104

    authors: Yu HK,Liu X,Chen JK,Wang S,Quan XY

    更新日期:2019-02-11 00:00:00

  • Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway.

    abstract::Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expressio...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00322

    authors: Zhang W,Ping J,Zhou Y,Chen G,Xu L

    更新日期:2019-04-11 00:00:00