Lipopolysaccharide, Mediator of Sepsis Enigma: Recognition and Signaling
Asma Bashir, Mujeeb Zaffar Banday, Ehtishamul Haq
International Journal of Biochemistry Research & Review · pp. 1–13 · Published 10 Feb 2011
10.9734/IJBCRR/2011/154Abstract
The outer leaflet of Gram-negative bacterial membrane contains a great amount of lipopolysaccharides, also known as endotoxins, which play a central role in the pathogenesis of sepsis and ultimately septic shock. Lipopolysaccharide (LPS) is potent inducer of acute sepsis or chronic inflammation. Sepsis can strike anyone, but is most likely to develop from infection associated with events such as pneumonia, trauma, surgery, and burns, or serious illnesses such as cancer and AIDS. In fact, people whose deaths are ascribed to complications of cancer, AIDS, or pneumonia, often actually die as a direct result of sepsis. Sepsis involves a complex interaction between bacterial toxins and the host immune system. LPS stimulates Toll-like receptor (TLR)-4 which leads to the formation and release of range of proinflammatory mediators which are essential for the potent immune response. The massive host response to this single bacterial pattern recognition molecule is sufficient to generate diffuse endothelial injury, tissue hypoperfusion, disseminated intravascular coagulation and refractory shock. LPS recognition involves LPS binding protein (LBP), CD14 ending up in TLR4/MD-2/LPS complex. The complex leads to activation of TLR4 and subsequent signaling cascade via two pathways i. e., myeloid differentiation protein 88 (MyD88)-dependent and TRIF-dependent. Here is a brief review of TLR4 signaling and LPS recognition biology with its impact if any on downstream pathways.
References (70)
- 1 Pathogen Recognition and Innate Immunity [DOI]
- 2 A human homologue of the Drosophila Toll protein signals activation of adaptive immunity [DOI]
- 3 CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding Protein [DOI]
- 4 Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway [DOI]
- 5 The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors [DOI]
- 6 Unresponsiveness of MyD88-Deficient Mice to Endotoxin [DOI]
- 7 TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β [DOI]
- 8 Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction [DOI]
- 9 Ubiquitin signalling in the NF-κB pathway [DOI]
- 10 TYPE I INTERFERONS (α/β) IN IMMUNITY AND AUTOIMMUNITY [DOI]
- 11 MyD88: An Adapter That Recruits IRAK to the IL-1 Receptor Complex [DOI]
- 12 Essential role of MD-2 in LPS responsiveness and TLR4 distribution [DOI]
- 13 Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6 [DOI]
- 14 Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response [DOI]
- 15 IRAK: A Kinase Associated with the Interleukin-1 Receptor [DOI]
- 16 RIP1 is an essential mediator of Toll-like receptor 3–induced NF-κB activation [DOI]
- 17 Phosphoinositide-Mediated Adaptor Recruitment Controls Toll-like Receptor Signaling [DOI]
- 18 IRF3 Mediates a TLR3/TLR4-Specific Antiviral Gene Program [DOI]
- 19 The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors [DOI]
- 20 TLR4, but not TLR2, mediates IFN-β–induced STAT1α/β-dependent gene expression in macrophages [DOI]
- 21 Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. [DOI]
- 22 IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase [DOI]
- 23 Structures of the Toll-like Receptor Family and Its Ligand Complexes [DOI]
- 24 Crystal Structures of Human MD-2 and Its Complex with Antiendotoxic Lipid IVa [DOI]
- 25 Mouse Toll-like Receptor 4·MD-2 Complex Mediates Lipopolysaccharide-mimetic Signal Transduction by Taxol [DOI]
- 26 The myristoylation of TRIF-related adaptor molecule is essential for Toll-like receptor 4 signal transduction [DOI]
- 27 Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling [DOI]
- 28 The role of Toll-like receptors in the host response to viruses [DOI]
- 29 ML — a conserved domain involved in innate immunity and lipid metabolism [DOI]
- 30 Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities [DOI]
- 31 Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation [DOI]
- 32 Lipopolysaccharide Binding Protein-mediated Complexation of Lipopolysaccharide with Soluble CD14 [DOI]
- 33 Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein. [DOI]
- 34 Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4 [DOI]
- 35 Catalytic Properties of Lipopolysaccharide (LPS) Binding Protein [DOI]
- 36 Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein Release Lipopolysaccharides from Gram-Negative Bacterial Membranes [DOI]
- 37 The expanding family of MyD88-like adaptors in Toll-like receptor signal transduction [DOI]
- 38 IRAK1 and IRAK4 Promote Phosphorylation, Ubiquitination, and Degradation of MyD88 Adaptor-like (Mal) [DOI]
- 39 Lipid IVA inhibits synthesis and release of tumor necrosis factor induced by lipopolysaccharide in human whole blood ex vivo. [DOI]
- 40 Ligand-Receptor and Receptor-Receptor Interactions Act in Concert to Activate Signaling in the Drosophila Toll Pathway [DOI]
- 41 Physicochemical properties of the lipopolysaccharide unit that activates B lymphocytes. [DOI]
- 42 The role of disulfide bonds in the assembly and function of MD-2 [DOI]
- 43 Mastoparan, a G Protein Agonist Peptide, Differentially Modulates TLR4- and TLR2-Mediated Signaling in Human Endothelial Cells and Murine Macrophages [DOI]
- 44 Endotoxin: physical requirements for cell activation [DOI]
- 45 Structure-function analysis of soluble and membrane-bound CD14.
- 46 Induction of human interleukin 1 by bacterial and synthetic lipid A [DOI]
- 47 Role of the physical state of Salmonella lipopolysaccharide in expression of biological and endotoxic properties [DOI]
- 48 CD14: Chaperone or Matchmaker? [DOI]
- 49 Newer aspects of the chemical structure and biological activity of bacterial endotoxins.
- 50 Approaching the Asymptote? Evolution and Revolution in Immunology [DOI]
- 51 Toll-like receptors in innate immunity [DOI]
- 52 Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway [DOI]
- 53 IKKε and TBK1 are essential components of the IRF3 signaling pathway [DOI]
- 54 A family of human receptors structurally related to Drosophila Toll [DOI]
- 55 Pyogenic Bacterial Infections in Humans with MyD88 Deficiency [DOI]
- 56 Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling [DOI]
- 57 Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran [DOI]
- 58 Structural basis for signal transduction by the Toll/interleukin-1 receptor domains [DOI]
- 59 Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-β (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-κB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling [DOI]
- 60 Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide [DOI]
- 61 Immune Cell Activation by Bacterial Cpg-DNA through Myeloid Differentiation Marker 88 and Tumor Necrosis Factor Receptor–Associated Factor (Traf)6 [DOI]
- 62 Heat Shock Protein gp96 Is a Master Chaperone for Toll-like Receptors and Is Important in the Innate Function of Macrophages [DOI]
- 63 IRAK-M Is a Novel Member of the Pelle/Interleukin-1 Receptor-associated Kinase (IRAK) Family [DOI]
- 64 The host type I interferon response to viral and bacterial infections [DOI]
- 65 Molecular Genetic Analysis of an Endotoxin Nonresponder Mutant Cell Line [DOI]
- 66 Dual Role of Lipopolysaccharide (LPS)-Binding Protein in Neutralization of LPS and Enhancement of LPS-Induced Activation of Mononuclear Cells [DOI]
- 67 A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses [DOI]
- 68 R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells [DOI]
- 69 Monomeric Re lipopolysaccharide from Escherichia coli is more active than the aggregated form in the Limulus amebocyte lysate assay and in inducing Egr-1 mRNA in murine peritoneal macrophages. [DOI]
- 70 Cutting Edge: The Induction of Acute Phase Proteins by Lipopolysaccharide Uses a Novel Pathway That Is CD14-Independent [DOI]
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