Cited by 1,442Immune Response and InflammationSepsis Diagnosis and TreatmentInflammation biomarkers and pathways

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Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin

Ulevitch, R J, Tobias, P S·1995·Annual Review of Immunology

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Abstract

In humans and experimental animals the presence of bacterial lipopolysaccharide (endotoxin, LPS) signals the presence of gram-negative bacteria. Recognition of LPS triggers gene induction by myeloid and nonmyeloid lineage cells. These inducible genes encode proteins that include cytokines, adhesive proteins, and enzymes that produce low molecular weight proinflammatory mediators. Together the products of these inducible genes upregulate host defense systems that participate in eliminating the bacterial infection. Unfortunately, these same mediators contribute to a serious human disease known as septic shock. Considerable progress has been made during the past decade in determining the sources, identities, and sequence of release of these mediators. In contrast, until recently, marked gaps in our knowledge existed regarding the identity of the LPS receptor and intracellular signaling pathways responsible for LPS-induced cell activation. The discovery in 1986 of a plasma protein termed LPS binding protein (LBP) led to the discovery of unanticipated mechanisms of LPS-induced cell activation. CD14 was found as a soluble serum protein or as a glycosylphosphatidylinositol (GPI)-anchored protein of myeloid lineage cells; it now occupies a key role in LPS-induced cell activation as we understand it today. Here we discuss how LBP enables LPS binding to CD14 and how complexes of LPS and soluble or GPI-anchored CD14 participate in cell activation. We also review the evidence supporting a model for a functional LPS receptor of myeloid cells, which is multimeric, comprised of GPI-anchored CD14 and a presently unidentified transmembrane protein that together bind LPS and initiate cell activation via kinase cascades.

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A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian Cells
Han, J., Lee, J. D., Bibbs, L., & Ulevitch, R. J. (1994) · Science · doi:10.1126/science.7914033 · Cited by 2,647
Self-citation
Structure and Function of Lipopolysaccharide Binding Protein
Schumann, R. R., Leong, S. R., Flaggs, G., Gray, P. W., Wright, S. D., Mathison, J. C., Tobias, P. S., & Ulevitch, R. J. (1990) · Science · doi:10.1126/science.2402637 · Cited by 1,672
Self-citation
The immune system evolved to discriminate infectious nonself from noninfectious self
Janeway, C. A. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90198-g · Cited by 1,343
Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria
Takeda, J., Miyata, T., Kawagoe, K., Iida, Y., Endo, Y., Fujita, T., Takahashi, M., Kitani, T., & Kinoshita, T. (1993) · Cell · doi:10.1016/0092-8674(93)90250-t · Cited by 1,059
A Divergence in the MAP Kinase Regulatory Network Defined by MEK Kinase and Raf
Lange-Carter, C. A., Pleiman, C. M., Gardner, A. M., Blumer, K. J., & Johnson, G. L. (1993) · Science · doi:10.1126/science.8385802 · Cited by 827
Potocytosis: Sequestration and Transport of Small Molecules by Caveolae
Anderson, R. G. W., Kamen, B. A., Rothberg, K. G., & Lacey, S. W. (1992) · Science · doi:10.1126/science.1310359 · Cited by 734
The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage.
Haziot, A., Chen, S., Ferrero, E., Low, M. G., Silber, R., & Goyert, S. M. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.2.547 · Cited by 645
Atomic structure of the MAP kinase ERK2 at 2.3 A resolution
Zhang, F., Strand, A., Robbins, D., Cobb, M. H., & Goldsmith, E. J. (1994) · Nature · doi:10.1038/367704a0 · Cited by 592
Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum.
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Gram‐negative endotoxin: an extraordinary lipid with profound effects on eukaryotic signal transduction 1
Raetz, C. R. H., Ulevitch, R. I., Wright, S. D., Sibley, C. H., Ding, A. H., & Nathan, C. (1991) · The FASEB Journal · doi:10.1096/fasebj.5.12.1916089 · Cited by 507
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“3) [105].”
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Self-citation
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Background
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“sCD14, detectable at high concentrations and constitutively present in the circulation (15), is believed to play a key role as intermediate in the neutralization of LPS under physiological conditions.”
Background
Rem Is a New Member of the Rad- and Gem/Kir Ras-related GTP-binding Protein Family Repressed by Lipopolysaccharide Stimulation
Finlin, B. S., & Andres, D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.21982 · Cited by 95
Lipopolysaccharide‐Binding Proteins and their Involvement in the Bacterial Clearance from the Hemolymph of the Silkworm Bombyx Mori
Koizumi, N., Morozumi, A., Imamura, M., Tanaka, E., Iwahana, H., & Sato, R. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.t01-1-00217.x · Cited by 94
Lipopolysaccharide-Induced Activation of β2-Integrin Function in Macrophages Requires Irak Kinase Activity, p38 Mitogen- Activated Protein Kinase, and the Rap1 GTPase
Schmidt, A., Caron, E., & Hall, A. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.2.438-448.2001 · Cited by 94
“CD14 lacks a cytoplasmic domain, and it has recently been suggested that LPS signals are transduced through members of the Toll receptor family (10, 26, 32, 42, 49, 50, 62).”
BackgroundInfluential
Host resistance to infection: genetic control of lipopolysaccharide responsiveness by TOLL-like receptor genes.
Qureshi, S., Gros, P., & Malo, D. (1999) · Trends in Genetics · doi:10.1016/s0168-9525(99)01782-5 · Cited by 99
Regulation of macrophage activation in alcoholic liver disease
Thakur, V., McMullen, M. R., Pritchard, M. T., & Nagy, L. E. (2007) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2006.04650.x · Cited by 93
Specific expression of antimicrobial peptide and HSP70 genes in response to heat-shock and several bacterial challenges in mussels
Cellura, C., Toubiana, M., Parrinello, N., & Roch, P. G. (2006) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2006.06.007 · Cited by 93
Cytokines and the lung
Toews, G. B. (2001) · European Respiratory Journal · doi:10.1183/09031936.01.00266001 · Cited by 91
Review: The lipemia of sepsis: triglyceride-rich lipoproteins as agents of innate immunity
Harris, H. W., Gosnell, J. E., & Kumwenda, Z. L. (2000) · Journal of Endotoxin Research · doi:10.1177/09680519000060060301 · Cited by 93
Regions of the Mouse CD14 Molecule Required for Toll-like Receptor 2- and 4-mediated Activation of NF-κB
Muroi, M., Ohnishi, T., & Tanamoto, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205966200 · Cited by 93
Overexpression of Toll-Like Receptor 4 Amplifies the Host Response to Lipopolysaccharide and Provides a Survival Advantage in Transgenic Mice
Bihl, F., Salez, L., Beaubier, M., Torres, D., Larivière, L., Laroche, L., Benedetto, A., Martel, D., Lapointe, J., Ryffel, B., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.12.6141 · Cited by 93
Innate Immune Response of Corneal Epithelial Cells to Staphylococcus aureus Infection: Role of Peptidoglycan in Stimulating Proinflammatory Cytokine Secretion
Kumar, A., Zhang, J., & Yu, F.-S. X. (2004) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.04-0467 · Cited by 127
“PGN is an alternating -linked N-acetylmuramyl and N-acetylglucosaminyl glycan whose residues are cross-linked by short peptides.(22,23) LTA is anchored in the membrane by glycolipids found in many Gram-positive bacteria(24) and has been shown to induce the ERK signaling pathway in the cornea.”
Effect of Phosphate Binders on Serum Inflammatory Profile, Soluble CD14, and Endotoxin Levels in Hemodialysis Patients
Navarro‐González, J. F., Fernández, C. M., de Fuentes, M. M., Donate‐Correa, J., Cazaña‐Perez, V., & García-Pérez, J. (2011) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.01650211 · Cited by 92
From the Cover: Exposure to Oral Antibiotics Induces Gut Microbiota Dysbiosis Associated with Lipid Metabolism Dysfunction and Low-Grade Inflammation in Mice
Jin, Y., Wu, Y., Zeng, Z., Jin, C., Wu, S., Wang, Y., & Fu, Z. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw150 · Cited by 93
Lipopolysaccharide Directly Stimulates the Intrapituitary Interleukin-6 Production by Folliculostellate Cells via Specific Receptors and the p38 Mitogen-Activated Protein Kinase/Nuclear Factor- B Pathway
Lohrer, P., Gloddek, J., Nagashima, A. C., Korali, Z., Hopfner, Ú., Páez-Pereda, M., ARZT, E. S., Stalla, G. K., & Renner, U. (2000) · Endocrinology · doi:10.1210/endo.141.12.7811 · Cited by 93
ROLE OF BACTERIAL ENDOTOXIN IN CHRONIC HEART FAILURE
Charalambous, B. M., Stephens, R. C. M., Feavers, I. M., & Montgomery, H. (2007) · Shock · doi:10.1097/shk.0b013e318033ebc5 · Cited by 91
Anti-inflammatory pathways and alcoholic liver disease: Role of an adiponectin/interleukin-10/heme oxygenase-1 pathway
Mandal, P. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i11.1330 · Cited by 92
RETRACTED: Dietary Bacillus subtilis-based direct-fed microbials alleviate LPS-induced intestinal immunological stress and improve intestinal barrier gene expression in commercial broiler chickens
Gadde, U. D., Oh, S., Lee, Y., Davis, E., Zimmerman, N. P., Rehberger, T. G., & Lillehoj, H. S. (2017) · Research in Veterinary Science · doi:10.1016/j.rvsc.2017.05.004 · Cited by 90
Retracted
Central role of dendritic cells in the regulation and deregulation of immune responses
Granucci, F., Zanoni, I., & Ricciardi‐Castagnoli, P. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8009-2 · Cited by 88
Endotoxin Interactions with Lipopolysaccharide‐Responsive Cells
Tobias, P. S., Tapping, R. I., & Gegner, J. A. (1999) · Clinical Infectious Diseases · doi:10.1086/515163 · Cited by 90
Self-citation
E6020: a synthetic Toll-like receptor 4 agonist as a vaccine adjuvant
Ishizaka, S. T., & Hawkins, L. D. (2007) · Expert Review of Vaccines · doi:10.1586/14760584.6.5.773 · Cited by 91
Heterogeneous Expression and Release of CD14 by Human Gingival Fibroblasts: Characterization and CD14-Mediated Interleukin-8 Secretion in Response to Lipopolysaccharide
Sugawara, S., Sugiyama, A., Nemoto, E., Rikiishi, H., & Takada, H. (1998) · Infection and Immunity · doi:10.1128/iai.66.7.3043-3049.1998 · Cited by 90
A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
Kang, Y., Kuang, X., Yan, H., Ren, P., Yang, X., Liu, H., Liu, Q., Yang, H., Kang, X., Shen, X., et al. (2023) · mSystems · doi:10.1128/msystems.01127-22 · Cited by 94
“LPS is a component of the Gram-negative bacterial cell wall and an endotoxin; its release results from the lysis of Gram-negative bacteria (33, 34).”
Background
Peptidoglycan-Induced IL-6 Production in RAW 264.7 Macrophages Is Mediated by Cyclooxygenase-2, PGE2/PGE4 Receptors, Protein Kinase A, IκB Kinase, and NF-κB
Chen, B.-C., Liao, C.-C., Hsu, M., Liao, Y., Lin, C., Sheu, J., & Lin, C. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.1.681 · Cited by 89
Neutrophil Activation by Bacterial Lipoprotein Versus Lipopolysaccharide: Differential Requirements for Serum and CD14
Soler-Rodriguez, A. M., Zhang, H., Lichenstein, H. S., Qureshi, N., Niesel, D. W., Crowe, S. E., Peterson, J. W., & Klimpel, G. R. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.5.2674 · Cited by 89
“This is not unique to LP since a CD14-independent stimulatory pathway also becomes apparent at progressively higher concentrations of LPS (75) and spirochetal lipoproteins (51).”
Background
Pterostilbene attenuates lipopolysaccharide-induced learning and memory impairment possibly via inhibiting microglia activation and protecting neuronal injury in mice
Hou, Y., Xie, G., Miao, F.-R., Ding, L., Mou, Y., Wang, L., Su, G., Chen, G., Yang, J., & Wu, C. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.03.015 · Cited by 90
“LPS mediates its effect through the CD14 receptor, which is expressed by monocytes and macrophages (Kim et al., 2005; Ulevitch and Tobias, 1995).”
Background
Lipoteichoic acid induces nuclear factor‐κB activation and nitric oxide synthase expression via phosphatidylinositol 3‐kinase, Akt, and p38 MAPK in RAW 264.7 macrophages
Kao, S., Lei, H., Kuo, C., Chang, M., Chen, B.-C., Chang, Y.-C., Chiu, W., & Lin, C. (2005) · Immunology · doi:10.1111/j.1365-2567.2005.02160.x · Cited by 89
Peptidoglycan Induces Nuclear Factor-κB Activation and Cyclooxygenase-2 Expression via Ras, Raf-1, and ERK in RAW 264.7 Macrophages
Chen, B.-C., Chang, Y.-S., Kang, J.-C., Hsu, M., Sheu, J., Chen, T.-L., Teng, C., & Lin, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311279200 · Cited by 87
Kohlenhydratmimetika: ein neuer Lösungsansatz für das Problem der kohlenhydratvermittelten biologischen Erkennung
Sears, P. S., & Wong, C. (1999) · Angewandte Chemie · doi:10.1002/(sici)1521-3757(19990816)111:16 · Cited by 89
Lipopolysaccharide-Induced Leukocyte Rolling and Adhesion in the Rat Mesenteric Microcirculation: Regulation by Glucocorticoids and Role of Cytokines
Davenpeck, K. L., Zagorski, J., Schleimer, R. P., & Bochner, B. S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.12.6861 · Cited by 89
The Pathophysiology of Graft‐Vs.‐Host Disease
Ferrara, J. L. M., & Antin, J. H. (2003) · Wiley eBooks · doi:10.1002/9780470987070.ch27 · Cited by 89
Breaking down the cell wall: Still an attractive antibacterial strategy
Zhou, J., Cai, Y., Liu, Y., An, H., Deng, K., Ashraf, M. A., Zou, L., & Wang, J. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.952633 · Cited by 99
“In the host, cluster of differentiation (CD) 14 (Ulevitch and Tobias, 1995) and Toll-like receptor (TLR)-4/Myeloid differentiation (MD) 2 complex (Kim et al.”
Background
The Carboxyl-terminal Domain of Closely Related Endotoxin-binding Proteins Determines the Target of Protein-Lipopolysaccharide Complexes
Iovine, N. M., Eastvold, J. S., Elsbach, P., Weiss, J. P., & Gioannini, T. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109622200 · Cited by 88
Protein-energy malnutrition decreases the expression of TLR-4/MD-2 and CD14 receptors in peritoneal macrophages and reduces the synthesis of TNF-α in response to lipopolysaccharide (LPS) in mice
Fock, R. A., Vinolo, M. A. R., Rocha, V., de Sá-Rocha, L. C., & Borelli, P. (2007) · Cytokine · doi:10.1016/j.cyto.2007.08.007 · Cited by 89
Identification and characterization of a myeloid differentiation factor 88 (MyD88) cDNA from Zhikong scallop Chlamys farreri
Qiu, L., Song, L., Yu, Y., Xu, W., Ni, D., & Zhang, Q. (2007) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2007.01.012 · Cited by 88
Interactions of CD14 with Components of Gram-Positive Bacteria
Dziarski, R., Ulmer, A. J., & Gupta, D. (1999) · KARGER eBooks · doi:10.1159/000058761 · Cited by 89
Role of p38 MAPK in ICAM-1 Expression of Vascular Endothelial Cells Induced by Lipopolysaccharide
Yan, W., Zhao, K., Jiang, Y., Huang, Q., Wang, J., Kan, W.-H., & Wang, S. (2002) · Shock · doi:10.1097/00024382-200205000-00016 · Cited by 88
“LPS from gram-negative bacterial cell walls is a key mediator that triggers shock and inflammatory responses, and can reach 100 to 1,000 pg/mL in plasma of endotoxic shock patients (less than 10 pg/mL in plasma of healthy persons) (2, 3).”
Background
Bacterial Lipopolysaccharide Can Enter Monocytes Via Two CD14-Dependent Pathways
Kitchens, R. L., Wang, P., & Munford, R. S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.10.5534 · Cited by 88

Authors: Ulevitch, R. J., & Tobias, P. S.
Affiliations: Scripps Research Institute (US)
ORCID: Ulevitch, R J
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 1995-04
Volume: 13
Issue: 1
Pages: 437-457
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev.iy.13.040195.002253
OpenAlex: W2113828544
Cited by: 1,442
References: 36
Citations by year: 2026: 4 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 25 · 2020: 23 · 2019: 21 · 2018: 22 · 2017: 24 · 2016: 37 · 2015: 29 · 2014: 39 · 2013: 43 · 2012: 38
FWCI: 20.96
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (GM28485, GM3769)
National Institute of Allergy and Infectious Diseases (AI 15136, R01AI015136)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: lipopolysaccharide, endotoxin, LPS receptor, CD14, LPS-binding protein, septic shock, myeloid cells, intracellular signaling, transmembrane proteins, pro-inflammatory mediators
MeSH terms: Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Amino Acid Sequence, Animals, Carbohydrate Sequence, Carrier Proteins, Humans, Lipopolysaccharides, Membrane Glycoproteins, Models, Biological, Molecular Sequence Data, Receptors, Immunologic, Shock, Septic, Antigens, Differentiation, Myelomonocytic, Molecular Structure, Signal Transduction, Antigens, CD, Calcium-Calmodulin-Dependent Protein Kinases, Lipopolysaccharide Receptors

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Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin

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