Endogenous and exogenous pathways maintain the reductive capacity of the phagosome.

Abstract:

:Although endosomes, lysosomes, and phagosomes require a reductive environment for the optimal activity of disulfide reductases and other thiol-dependent enzymes, how these reductive environments are established and maintained remain unknown. Our goal in this study was to begin to elucidate the redox control systems responsible for maintaining redox-sensitive enzymatic activities in the phagolysosome of murine macrophages. Through the use of specific inhibitors and genetic knockdown of known redox enzymes, we identified redox pathways that influence phagosomal disulfide reduction. In particular, known inhibitors of the NADPH-dependent selenoprotein, thioredoxin reductase, were shown to inhibit phagosomal disulfide reduction and phagosomal proteolysis. This was supported by the observation that conditional deletion of the selenocysteine tRNA in macrophages decreased phagosomal disulfide reduction capacity. In addition, pharmacologic inhibition of the pentose phosphate pathway decreased rates of disulfide reduction and proteolysis in the phagosome, implicating NADPH as a source of phagosomal reductive energy. Finally, by analyzing the effect of extracellular redox couples, such as cysteine:cystine on thiol-dependent phagosomal processes, we demonstrated that the extracellular space can additionally supply the phagosome with reductive energy. Collectively, these data demonstrate that defined cytosolic reductive pathways act in concert with the uptake of cysteine from the extracellular space to support thiol-dependent chemistries in the phagosome.

journal_name

J Leukoc Biol

authors

Balce DR,Greene CJ,Tailor P,Yates RM

doi

10.1189/jlb.2HI0315-083R

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

17-26

issue

1

eissn

0741-5400

issn

1938-3673

pii

jlb.2HI0315-083R

journal_volume

100

pub_type

杂志文章
  • A new role for monoamine oxidases in the modulation of macrophage-inducible nitric oxide synthase gene expression.

    abstract::This report focuses on the modulatory role of endogenous H(2)O(2) on lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-induced inducible nitric oxide synthase (NOS2) gene expression in rat peritoneal macrophages. Exogenously added H(2)O(2) was initially found to inhibit the synthesis of NOS2, which prompted us to ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1003459

    authors: Vega A,Chacón P,Monteseirín J,El Bekay R,Alvarez M,Alba G,Conde J,Martín-Nieto J,Bedoya FJ,Pintado E,Sobrino F

    更新日期:2004-06-01 00:00:00

  • Cloning and characterization of a novel cDNA that is IFN-gamma-induced in mouse peritoneal macrophages and encodes a putative GTP-binding protein.

    abstract::Macrophage activation by IFN-gamma results in a cascade of gene expression. To identify genes activated in mouse peritoneal macrophages by IFN-gamma, we created a cDNA subtraction library of IFN-gamma-induced genes. We have isolated from this subtraction library a novel cDNA clone, called Mg21, whose mRNA is absent in...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.57.3.477

    authors: Lafuse WP,Brown D,Castle L,Zwilling BS

    更新日期:1995-03-01 00:00:00

  • TLR3 impairment in human newborns.

    abstract::Newborns are highly susceptible to viral infections. We hypothesized that this susceptibility could be due to a dysregulated expression of innate virus-sensing receptors, i.e., TLR3, TLR7, TLR8, and TLR9 and the cytosolic receptors retinoic acid-inducible gene I, melanoma differentiation-associated protein 5, protein ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1212617

    authors: Slavica L,Nordström I,Karlsson MN,Valadi H,Kacerovsky M,Jacobsson B,Eriksson K

    更新日期:2013-11-01 00:00:00

  • Phagosome dynamics during phagocytosis by neutrophils.

    abstract::The neutrophil is a key player in immunity, and its activities are essential for the resolution of infections. Neutrophil-pathogen interactions usually trigger a large arsenal of antimicrobial measures that leads to the highly efficient killing of pathogens. In neutrophils, the phagocytic process, including the format...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0810457

    authors: Nordenfelt P,Tapper H

    更新日期:2011-08-01 00:00:00

  • H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated stimulations, and resistance to activation-induced apoptosis during T cell response to mycobacterial antigens.

    abstract::Genetic variation in the major histocompatibility complex (MHC) influences susceptibility and immune responses to Mycobacterium tuberculosis in mice and humans, but connections among the severity of tuberculosis (TB), dynamic changes in T cell responses to mycobacteria, and MHC genetic polymorphisms are poorly charact...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0705392

    authors: Pichugin AV,Petrovskaya SN,Apt AS

    更新日期:2006-04-01 00:00:00

  • Activation of EphA receptors on CD4+CD45RO+ memory cells stimulates migration.

    abstract::We have demonstrated previously that binding of ephrin-A1 to EphA receptors on human CD4(+) and CD8(+) T cells stimulates migration. Two EphA receptors have been reported in T cells: EphA1 at the protein level and EphA4 at the mRNA level. In this study, we wanted to investigate the expression profile of these receptor...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0709497

    authors: Holen HL,Nustad K,Aasheim HC

    更新日期:2010-06-01 00:00:00

  • Phagocytosis of gram-negative bacteria by a unique CD14-dependent mechanism.

    abstract::THP-1-derived cell lines were stably transfected with constructs encoding glycophosphatidylinositol (GPI)-anchored or transmembrane forms of human CD14. CD14 expression was associated with enhanced phagocytosis of serum (heat-inactivated)-opsonized Escherichia coli (opEc). Both the GPI-anchored and transmembrane forms...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.62.6.786

    authors: Schiff DE,Kline L,Soldau K,Lee JD,Pugin J,Tobias PS,Ulevitch RJ

    更新日期:1997-12-01 00:00:00

  • CD4+/CD8+ double-positive T cells: more than just a developmental stage?

    abstract::CD4(+)/CD8(+) DP thymocytes are a well-described T cell developmental stage within the thymus. However, once differentiated, the CD4(+) lineage or the CD8(+) lineage is generally considered to be fixed. Nevertheless, mature CD4(+)/CD8(+) DP T cells have been described in the blood and peripheral lymphoid tissues of nu...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.1RU0814-382

    authors: Overgaard NH,Jung JW,Steptoe RJ,Wells JW

    更新日期:2015-01-01 00:00:00

  • Intravital imaging of eosinophils: Unwrapping the enigma.

    abstract::Eosinophils are traditionally associated with allergic and parasitic inflammation. More recently, eosinophils have also been shown to have roles in diverse processes including development, intestinal health, thymic selection, and B-cell survival with the majority of these insights being derived from murine models and ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.3HR0220-396R

    authors: Nguyen WNT,Jacobsen EA,Finney CAM,Colarusso P,Patel KD

    更新日期:2020-07-01 00:00:00

  • Endotoxin tolerance attenuates LPS-induced TLR4 mobilization to lipid rafts: a condition reversed by PKC activation.

    abstract::Endotoxin tolerance is characterized by attenuated macrophage activation to subsequent LPS challenge and can be reversed through nonspecific protein kinase C (PKC) activation, and activation by LPS within naïve cells requires the activation of the cell surface receptors CD14 and TLR4 on lipid rafts. The effect of PKC ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0106053

    authors: Cuschieri J,Billigren J,Maier RV

    更新日期:2006-12-01 00:00:00

  • Neutrophil antimicrobial defense against Staphylococcus aureus is mediated by phagolysosomal but not extracellular trap-associated cathelicidin.

    abstract::Neutrophils kill invading pathogens by AMPs, including cathelicidins, ROS, and NETs. The human pathogen Staphylococcus aureus exhibits enhanced resistance to neutrophil AMPs, including the murine cathelicidin CRAMP, in part, as a result of alanylation of teichoic acids by the dlt operon. In this study, we took advanta...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0209053

    authors: Jann NJ,Schmaler M,Kristian SA,Radek KA,Gallo RL,Nizet V,Peschel A,Landmann R

    更新日期:2009-11-01 00:00:00

  • Neutrophil accumulation and plasma leakage induced in vivo by neutrophil-activating peptide-1.

    abstract::Neutrophil accumulation and plasma leakage induced in rabbit skin by neutrophil-activating peptide-1 (NAP-1, a 72 amino acid peptide produced by monocytes and a variety of tissue cells), E. coli endotoxin, and interleukin-1 (IL-1) were compared. Neutrophil accumulation at sites injected with NAP-1 was intense, rapid, ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.48.2.129

    authors: Colditz IG,Zwahlen RD,Baggiolini M

    更新日期:1990-08-01 00:00:00

  • From top to bottom: midkine and pleiotrophin as emerging players in immune regulation.

    abstract::Cytokines are pivotal in the generation and resolution of the inflammatory response. The midkine/pleiotrophin (MK/PTN) family of cytokines, composed of just two members, was discovered as heparin-binding neurite outgrowth-promoting factors. Since their discovery, expression of this cytokine family has been reported in...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.3MR1116-475R

    authors: Sorrelle N,Dominguez ATA,Brekken RA

    更新日期:2017-08-01 00:00:00

  • Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library.

    abstract::Neutrophil activation is a multistep process. In vitro activation of neutrophils with semiphysiological activators is optimal only after preactivation or priming with cytokines, chemotaxins, and/or bacterial products. Until now, no antibodies have been developed that can distinguish between resting and (cytokine) prim...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Koenderman L,Kanters D,Maesen B,Raaijmakers J,Lammers JW,de Kruif J,Logtenberg T

    更新日期:2000-07-01 00:00:00

  • Inhibition of fms-like tyrosine kinase 3 alleviates experimental arthritis by reducing formation of dendritic cells and antigen presentation.

    abstract::TKs are intracellular signaling molecules essential for cell homeostasis. Inhibition of TKs is used in treatment of malignancies and diabetes mellitus. The present study evaluated the role of Flt3 in antigen-induced arthritis. Mice were immunized with mBSA, and arthritis was induced by an i.a. injection of mBSA. Treat...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1110640

    authors: Dehlin M,Andersson S,Erlandsson M,Brisslert M,Bokarewa M

    更新日期:2011-10-01 00:00:00

  • Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis.

    abstract::Angiogenesis is essential in many physiological and pathological processes and can be stimulated by many different factors. To better understand and to manipulate this process more effectively, it would be beneficial to identify molecules common to the signaling pathways stimulated by different classes of angiogenic f...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0304175

    authors: Yao M,Zhou RH,Petreaca M,Zheng L,Shyy J,Martins-Green M

    更新日期:2006-09-01 00:00:00

  • Monocyte/macrophage traffic in HIV and SIV encephalitis.

    abstract::This short review focuses on the role of central nervous system (CNS) perivascular macrophages as targets of productive infection of the CNS. Data discussed include the importance of these cells as early targets of infection and their productive infection with AIDS. Many of the immune molecules on perivascular macroph...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0503207

    authors: Kim WK,Corey S,Alvarez X,Williams K

    更新日期:2003-11-01 00:00:00

  • Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation.

    abstract::Naïve T cells, when activated by specific antigen and cytokines, up-regulate adhesion molecules as well as chemokine receptors on their surface, which allows them to migrate to inflamed tissues. Human studies have shown that CXCR3 is one of the chemokine receptors that is induced during T cell activation. Moreover, CX...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1102573

    authors: Xie JH,Nomura N,Lu M,Chen SL,Koch GE,Weng Y,Rosa R,Di Salvo J,Mudgett J,Peterson LB,Wicker LS,DeMartino JA

    更新日期:2003-06-01 00:00:00

  • Differential effects of 15-deoxy-delta(12,14)-prostaglandin J2 and a peroxisome proliferator-activated receptor gamma agonist on macrophage activation.

    abstract::Prostaglandin J2 metabolite 15-deoxy-delta(12,14)-prostaglandin J2 (15-PGJ2) appears to possess anti-inflammatory properties. Unlike other prostaglandins, it has no known plasma membrane receptor. Its effects have been thought to occur through activation of the nuclear peroxisome proliferator-activated receptor gamma ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Guyton K,Bond R,Reilly C,Gilkeson G,Halushka P,Cook J

    更新日期:2001-04-01 00:00:00

  • Notch signaling in the immune system.

    abstract::Notch signaling plays a preeminent role during development in not only regulating cell fate decisions, but it can also influence growth and survival of progenitor cells. In the immune system, Notch is required for the maintenance of hematopoietic stem cells and in directing T- versus B-lineage commitment. In this revi...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0303089

    authors: Hoyne GF

    更新日期:2003-12-01 00:00:00

  • Oxygen metabolism of the HL-60 cell line: comparison of the effects of monocytoid and neutrophilic differentiation.

    abstract::HL-60 cells are promyelocytic leukemia cells that respond to culture conditions with differentiation into granulocytelike or macrophagelike phagocytes. O2 metabolism is critical to the microbicidal function of phagocytic cells. O2 metabolism was studied in HL-60 cells differentiated with dimethylsulfoxide (Me2SO) and ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.43.2.140

    authors: Thompson BY,Sivam G,Britigan BE,Rosen GM,Cohen MS

    更新日期:1988-02-01 00:00:00

  • Neutrophil-derived matrix metalloproteinase-9 is a potent activator of trypsinogen in acinar cells in acute pancreatitis.

    abstract::MMPs are generally considered to regulate degradation and remodeling of the ECM. Convincing data also implicate a role for MMPs in inflammatory conditions, such as AP, although the mechanisms are not known. The aim of this study was to define the role of MMPs in regulating activation of trypsinogen and tissue damage i...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0811443

    authors: Awla D,Abdulla A,Syk I,Jeppsson B,Regnér S,Thorlacius H

    更新日期:2012-05-01 00:00:00

  • Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-beta, and CTLA4Ig).

    abstract::There is growing evidence that, in addition to their role as initiators of immune responses, dendritic cells (DC) can exhibit tolerogenic properties. Immature DC deficient in cell surface costimulatory/accessory molecules can prolong organ and pancreatic islet allograft survival, whereas in vitro manipulation of DC by...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.66.2.293

    authors: Lu L,Lee WC,Takayama T,Qian S,Gambotto A,Robbins PD,Thomson AW

    更新日期:1999-08-01 00:00:00

  • Combined activation of innate and T cell immunity for recognizing immunomodulatory properties of therapeutic agents.

    abstract::Complex syndromes such as atherosclerosis and type 2 diabetes are disorders that are associated with inflammatory processes involving innate and adaptive immunity. Emerging knowledge about the pathological consequences of immune imbalances in a wide range of disease settings is expected to help to identify novel thera...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1003454

    authors: Rose B,Herder C,Löffler H,Kolb H,Martin S

    更新日期:2004-04-01 00:00:00

  • Detection of the production of oxygen-centered free radicals by human neutrophils using spin trapping techniques: a critical perspective.

    abstract::Human neutrophils generate oxygen reduction products as a consequence of membrane interactions with a number of stimuli. One oxygen-centered free radical (superoxide) has been unequivocally shown to result from this "respiratory burst," and some experimental evidence for another (hydroxyl radical) has been published, ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.41.4.349

    authors: Britigan BE,Cohen MS,Rosen GM

    更新日期:1987-04-01 00:00:00

  • Differential production of IFN-alpha/beta by CSF-1- and GM-CSF-derived macrophages.

    abstract::Mature macrophages, derived in vitro from bone marrow progenitors under the influence of either macrophage colony stimulating factor (CSF-1) or granulocyte-macrophage (GM)-CSF, have been shown to differ morphologically and functionally. The data presented in this report demonstrate that macrophages derived from bone m...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.48.1.43

    authors: Falk LA,Vogel SN

    更新日期:1990-07-01 00:00:00

  • Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163.

    abstract::CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Hintz KA,Rassias AJ,Wardwell K,Moss ML,Morganelli PM,Pioli PA,Givan AL,Wallace PK,Yeager MP,Guyre PM

    更新日期:2002-10-01 00:00:00

  • Common methodology is inadequate for studies on the microbicidal activity of neutrophils.

    abstract::Microbicidal activity of neutrophils is usually measured by colony-counting techniques after cell lysis in distilled water. While studying the effect of the reduced nicotinamide adenine dinucleotide phosphate-oxidase inhibitor diphenyleneiodonium (DPI) on the staphylocidal activity of neutrophils, we obtained inconsis...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0605338

    authors: Decleva E,Menegazzi R,Busetto S,Patriarca P,Dri P

    更新日期:2006-01-01 00:00:00

  • Alcohol enhances symptoms and propensity for infection in inflammatory bowel disease patients and a murine model of DSS-induced colitis.

    abstract::Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammat...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.4MA1217-506R

    authors: Cannon AR,Kuprys PV,Cobb AN,Ding X,Kothari AN,Kuo PC,Eberhardt JM,Hammer AM,Morris NL,Li X,Choudhry MA

    更新日期:2018-09-01 00:00:00

  • Leukosialin (CD43) behavior during adhesion of human monocytic THP-1 cells to red blood cells.

    abstract::To understand the modulation and the behavior of glycocalyx elements during adhesion, we explored one of its components, the CD43 molecule, on human monocytic THP-1 cells exposed to cytokine stimulation and its redistribution during heterotypic adhesion to opsonized erythrocytes. First we demonstrated by immunofluores...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.61.5.609

    authors: Soler M,Merant C,Servant C,Fraterno M,Allasia C,Lissitzky JC,Bongrand P,Foa C

    更新日期:1997-05-01 00:00:00