Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin.

Abstract:

:Tumor necrosis factors (TNF) alpha and beta are structurally related cytokines that mediate a wide range of immunological, inflammatory, and cytotoxic effects. During bacterial infection of the bloodstream (sepsis), TNF-alpha induction by bacterial endotoxin is thought to be a major factor contributing to the cardiovascular collapse and critical organ failure that can develop. Despite antibiotic therapy, these consequences of sepsis continue to have a high mortality rate in humans. Here we describe a potent TNF antagonist, a TNF receptor (TNFR) immunoadhesin, constructed by gene fusion of the extracellular portion of human type 1 TNFR with the constant domains of human IgG heavy chain (TNFR-IgG). When expressed in transfected human cells, TNFR-IgG is secreted as a disulfide-bonded homodimer. Purified TNFR-IgG binds to both TNF-alpha and TNF-beta and exhibits 6- to 8-fold higher affinity for TNF-alpha than cell surface or soluble TNF receptors. In vitro, TNFR-IgG blocks completely the cytolytic effect of TNF-alpha or TNF-beta on actinomycin D-treated cells and is markedly more efficient than soluble TNFR (24-fold) or monoclonal anti-TNF-alpha antibodies (4-fold) in inhibiting TNF-alpha. In vitro, TNFR-IgG prevents endotoxin-induced lethality in mice when given 0.5 hr prior to endotoxin and provides significant protection when given up to 1 hr after endotoxin challenge. These results confirm the importance of TNF-alpha in the pathogenesis of septic shock and suggest a clinical potential for TNFR-IgG as a preventive and therapeutic treatment in sepsis.

authors

Ashkenazi A,Marsters SA,Capon DJ,Chamow SM,Figari IS,Pennica D,Goeddel DV,Palladino MA,Smith DH

doi

10.1073/pnas.88.23.10535

subject

Has Abstract

pub_date

1991-12-01 00:00:00

pages

10535-9

issue

23

eissn

0027-8424

issn

1091-6490

journal_volume

88

pub_type

杂志文章
  • Wolbachia as a bacteriocyte-associated nutritional mutualist.

    abstract::Many insects are dependent on bacterial symbionts that provide essential nutrients (ex. aphid-Buchnera and tsetse-Wiglesworthia associations), wherein the symbionts are harbored in specific cells called bacteriocytes that constitute a symbiotic organ bacteriome. Facultative and parasitic bacterial symbionts like Wolba...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0911476107

    authors: Hosokawa T,Koga R,Kikuchi Y,Meng XY,Fukatsu T

    更新日期:2010-01-12 00:00:00

  • Visualization of a primary anti-tumor immune response by positron emission tomography.

    abstract::Current methodologies that monitor immune responses rely on invasive techniques that sample tissues at a given point in time. New technologies are needed to elucidate the temporal patterns of immune responses and the spatial distribution of immune cells on a whole-body scale. We describe a noninvasive, quantitative, a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0508698102

    authors: Shu CJ,Guo S,Kim YJ,Shelly SM,Nijagal A,Ray P,Gambhir SS,Radu CG,Witte ON

    更新日期:2005-11-29 00:00:00

  • Pol31 and Pol32 subunits of yeast DNA polymerase δ are also essential subunits of DNA polymerase ζ.

    abstract::Replication through a diverse array of DNA lesions occurs by the sequential action of two translesion synthesis (TLS) DNA polymerases (Pols), in which one inserts the nucleotide opposite the lesion and the other carries out the subsequent extension. By extending from the nucleotide inserted by another Pol, Polζ plays ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1206052109

    authors: Johnson RE,Prakash L,Prakash S

    更新日期:2012-07-31 00:00:00

  • Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide.

    abstract::Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1801253115

    authors: Liu BH,Jobichen C,Chia CSB,Chan THM,Tang JP,Chung TXY,Li J,Poulsen A,Hung AW,Koh-Stenta X,Tan YS,Verma CS,Tan HK,Wu CS,Li F,Hill J,Joy J,Yang H,Chai L,Sivaraman J,Tenen DG

    更新日期:2018-07-24 00:00:00

  • Inactivation of ethanol-inducible cytochrome P450 and other microsomal P450 isozymes by trans-4-hydroxy-2-nonenal, a major product of membrane lipid peroxidation.

    abstract::Of the microsomal P450 cytochromes, the ethanol-inducible isoform, P450 2E1, is believed to be predominant in leading to oxidative damage, including the generation of radical species that contribute to lipid peroxidation, and in the reductive beta-scission of lipid hydroperoxides to give hydrocarbons and aldehydes. In...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.9.3764

    authors: Bestervelt LL,Vaz AD,Coon MJ

    更新日期:1995-04-25 00:00:00

  • Peripheral tolerance can be modified by altering KLF2-regulated Treg migration.

    abstract::Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolera...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1605849113

    authors: Pabbisetty SK,Rabacal W,Volanakis EJ,Parekh VV,Olivares-Villagómez D,Cendron D,Boyd KL,Van Kaer L,Sebzda E

    更新日期:2016-08-09 00:00:00

  • Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.

    abstract::Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40-kDa glycoprotein associated with human carcinomas of various origins. Molecular clones for the GA733-2 antigen were isolated from a colorectal carcinoma cell line cDNA library using the high-efficiency COS cell expression system. A 1.4-kilo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.9.3542

    authors: Szala S,Froehlich M,Scollon M,Kasai Y,Steplewski Z,Koprowski H,Linnenbach AJ

    更新日期:1990-05-01 00:00:00

  • Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood.

    abstract::Cytotoxic T lymphocyte antigen-4 (CTLA-4) is essential for immunological (self-) tolerance, but due to the early fatality of CTLA-4 KO mice, its specific function in central and peripheral tolerance and in different systemic diseases remains to be determined. Here, we further examined the role of CTLA-4 by abrogating ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1603892113

    authors: Klocke K,Sakaguchi S,Holmdahl R,Wing K

    更新日期:2016-04-26 00:00:00

  • In vivo imaging of calcium accumulation in fly interneurons as elicited by visual motion stimulation.

    abstract::The computation of motion plays a central role in visual orientation. The fly has been successfully used as a model system for analyzing the mechanisms underlying motion detection. Thereby, much attention has been paid to a neuronal circuit of individually identifiable neurons in the third visual ganglion that extract...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.9.4139

    authors: Borst A,Egelhaaf M

    更新日期:1992-05-01 00:00:00

  • The surface oxidation potential of human neuromelanin reveals a spherical architecture with a pheomelanin core and a eumelanin surface.

    abstract::Neuromelanin (NM) isolated from the substantia nigra region of the human brain was studied by scanning probe and photoelectron emission microscopies. Atomic force microscopy reveals that NM granules are comprised of spherical structures with a diameter of approximately 30 nm, similar to that observed for Sepia cuttlef...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0604010103

    authors: Bush WD,Garguilo J,Zucca FA,Albertini A,Zecca L,Edwards GS,Nemanich RJ,Simon JD

    更新日期:2006-10-03 00:00:00

  • Insulin-like growth factor II signaling through the insulin-like growth factor II/mannose-6-phosphate receptor promotes exocytosis in insulin-secreting cells.

    abstract::The insulin-like growth factor II (IGF-II)/mannose-6-phosphate (M-6-P) receptor is known to participate in endocytosis as well as sorting of lysosomal enzymes and is involved in membrane trafficking through rapid cycling between cytosolic membrane compartments and the plasma membrane. Here we demonstrate that IGF-II, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.12.6232

    authors: Zhang Q,Tally M,Larsson O,Kennedy RT,Huang L,Hall K,Berggren PO

    更新日期:1997-06-10 00:00:00

  • Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics.

    abstract::Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acut...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1420822111

    authors: Gawad C,Koh W,Quake SR

    更新日期:2014-12-16 00:00:00

  • Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein.

    abstract::In 1000 primary gastric carcinomas, 70 (7.0%) contained Epstein-Barr virus (EBV) genomic sequences detected by PCR and Southern blots. The positive tumors comprised 8 of 9 (89%) undifferentiated lymphoepithelioma-like carcinomas, 27 of 476 (5.7%) poorly differentiated adenocarcinomas, and 35 of 515 (6.8%) moderately t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.19.9131

    authors: Imai S,Koizumi S,Sugiura M,Tokunaga M,Uemura Y,Yamamoto N,Tanaka S,Sato E,Osato T

    更新日期:1994-09-13 00:00:00

  • Studies of transfer RNA tertiary structure by singlet-singlet energy transfer.

    abstract::This distance between a base next to the anticodon of tRNA and the 3' CpCpA terminus of the molecule has been estimated by singlet-singlet energy transfer experiments. The energy donor was the Y base of unknown structure found in yeast tRNA(phe). Three different energy acceptors were used: acriflavine, proflavinyl ace...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.65.1.39

    authors: Beardsley K,Cantor CR

    更新日期:1970-01-01 00:00:00

  • NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide.

    abstract::In animals, successful production of the visual chromophore (11-cis-retinal or derivatives thereof such as 11-cis-3-hydroxy-retinal) is essential for photoreceptor cell function and survival. These carotenoid-derived compounds must combine with a protein moiety (the opsin) to establish functional visual pigments. Evid...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0807805105

    authors: Oberhauser V,Voolstra O,Bangert A,von Lintig J,Vogt K

    更新日期:2008-12-02 00:00:00

  • A contact-insensitive subpopulation in Syrian hamster cell cultures with a greater susceptibility to chemically induced neoplastic transformation.

    abstract::We previously have identified a subpopulation of contact-insensitive (CS-) cells which lacks density-dependent inhibition of cell division in primary and low-passage cultures of Syrian hamster embryonic (SHE) fibroblastic cells. Further, we have shown that the proportion of these CS- cells declines as a result of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.15.5005

    authors: Nakano S,Ueo H,Bruce SA,Ts'o PO

    更新日期:1985-08-01 00:00:00

  • Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in Caenorhabditis elegans.

    abstract::Type II platelet-activating factor-acetylhydrolase [PAF-AH (II)] is an N-myristoylated enzyme that contains a lipase/esterase catalytic motif and selectively hydrolyzes the sn-2 acetyl ester of PAF and other short-chain acyl groups attached to phosphoglycerides. However, the physiological role of this enzyme remains t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0405507101

    authors: Inoue T,Sugimoto A,Suzuki Y,Yamamoto M,Tsujimoto M,Inoue K,Aoki J,Arai H

    更新日期:2004-09-07 00:00:00

  • Mutations in the HIV-1 envelope glycoprotein can broadly rescue blocks at multiple steps in the virus replication cycle.

    abstract::The p6 domain of HIV-1 Gag contains highly conserved peptide motifs that recruit host machinery to sites of virus assembly, thereby promoting particle release from the infected cell. We previously reported that mutations in the YPXnL motif of p6, which binds the host protein Alix, severely impair HIV-1 replication. Pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1820333116

    authors: Van Duyne R,Kuo LS,Pham P,Fujii K,Freed EO

    更新日期:2019-04-30 00:00:00

  • Intracellular antibody receptor TRIM21 prevents fatal viral infection.

    abstract::Host species have evolved mechanisms that can inhibit pathogen replication even after a cell has been successfully invaded. Here we show that tripartite-motif protein 21 (TRIM21), a ubiquitously expressed E3 ubiquitin ligase that targets viruses inside the cytosol, protects mice against fatal viral infection. Upon inf...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1301918110

    authors: Vaysburd M,Watkinson RE,Cooper H,Reed M,O'Connell K,Smith J,Cruickshanks J,James LC

    更新日期:2013-07-23 00:00:00

  • Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.

    abstract::A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1220832110

    authors: Ardehali R,Ali SR,Inlay MA,Abilez OJ,Chen MQ,Blauwkamp TA,Yazawa M,Gong Y,Nusse R,Drukker M,Weissman IL

    更新日期:2013-02-26 00:00:00

  • A peptide composed of tandem analogs of two myasthenogenic T cell epitopes interferes with specific autoimmune responses.

    abstract::Myasthenia gravis (MG) is a T cell-regulated, antibody-mediated autoimmune disease. Two peptides representing sequences of the human acetylcholine receptor alpha-subunit, p195-212 and p259-271, were previously shown to stimulate peripheral blood lymphocytes of patients with MG and were found to be immunodominant T cel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.7.3200

    authors: Katz-Levy Y,Paas-Rozner M,Kirshner S,Dayan M,Zisman E,Fridkin M,Wirguin I,Sela M,Mozes E

    更新日期:1997-04-01 00:00:00

  • Conserved methionine dictates substrate preference in Nramp-family divalent metal transporters.

    abstract::Natural resistance-associated macrophage protein (Nramp) family transporters catalyze uptake of essential divalent transition metals like iron and manganese. To discriminate against abundant competitors, the Nramp metal-binding site should favor softer transition metals, which interact either covalently or ionically w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1607734113

    authors: Bozzi AT,Bane LB,Weihofen WA,McCabe AL,Singharoy A,Chipot CJ,Schulten K,Gaudet R

    更新日期:2016-09-13 00:00:00

  • Recent acceleration in coastal cliff retreat rates on the south coast of Great Britain.

    abstract::Rising sea levels and increased storminess are expected to accelerate the erosion of soft-cliff coastlines, threatening coastal infrastructure and livelihoods. To develop predictive models of future coastal change we need fundamentally to know how rapidly coasts have been eroding in the past, and to understand the dri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1613044113

    authors: Hurst MD,Rood DH,Ellis MA,Anderson RS,Dornbusch U

    更新日期:2016-11-22 00:00:00

  • Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms.

    abstract::Siglecs are a recently discovered family of animal lectins that belong to the Ig superfamily and recognize sialic acids (Sias). CD33-related Siglecs (CD33rSiglecs) are a subgroup with as-yet-unknown functions, characterized by sequence homology, expression on innate immune cells, conserved cytosolic tyrosine-based sig...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0404833101

    authors: Angata T,Margulies EH,Green ED,Varki A

    更新日期:2004-09-07 00:00:00

  • Oxymetry deep in tissues with low-frequency electron paramagnetic resonance.

    abstract::We have measured the oxygen concentration in the body water of murine FSa and NFSa fibrosarcomas using a new method for quantitative oxygen concentration determination deep in the tissues of a living animal. The measurement uses unusually low-frequency electron paramagnetic spectroscopy sensitive to substrate 7 cm dee...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.26.13047

    authors: Halpern HJ,Yu C,Peric M,Barth E,Grdina DJ,Teicher BA

    更新日期:1994-12-20 00:00:00

  • A maize sesquiterpene cyclase gene induced by insect herbivory and volicitin: characterization of wild-type and mutant alleles.

    abstract::Plants can defend themselves from herbivorous insects by emitting volatile chemical signals that attract natural enemies of the herbivore. For example, maize seedlings attacked by beet armyworm larvae (Spodoptera exigua) produce a mixture of terpenoid and indole volatiles that serve to attract parasitic wasps. A key s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.240284097

    authors: Shen B,Zheng Z,Dooner HK

    更新日期:2000-12-19 00:00:00

  • Human genetic variation altering anthrax toxin sensitivity.

    abstract::The outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. Some host genes encode defense mechanisms, whereas others assist pathogen functions. Genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1121006109

    authors: Martchenko M,Candille SI,Tang H,Cohen SN

    更新日期:2012-02-21 00:00:00

  • nit-2, the major positive-acting nitrogen regulatory gene of Neurospora crassa, encodes a sequence-specific DNA-binding protein.

    abstract::The nit-2 major nitrogen regulatory gene of Neurospora crassa turns on the expression of various unlinked structural genes that specify nitrogen-catabolic enzymes under nitrogen-limitation conditions. The nit-2 gene encodes a protein of 1036 amino acid residues with a single zinc finger and a downstream basic region t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.14.5331

    authors: Fu YH,Marzluf GA

    更新日期:1990-07-01 00:00:00

  • Independent circuits in the basal ganglia for the evaluation and selection of actions.

    abstract::The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1314815110

    authors: Stephenson-Jones M,Kardamakis AA,Robertson B,Grillner S

    更新日期:2013-09-17 00:00:00

  • Target inference from collections of genomic intervals.

    abstract::Finding regions of the genome that are significantly recurrent in noisy data are a common but difficult problem in present day computational biology. Cores of recurrent events (CORE) is a computational approach to solving this problem that is based on a formalized notion by which "core" intervals explain the observed ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1306909110

    authors: Krasnitz A,Sun G,Andrews P,Wigler M

    更新日期:2013-06-18 00:00:00