Abstract:
:Lipid X, a precursor in the biosynthesis of lipid A, has been claimed to possess most of the immunostimulatory activity but none of the toxicity of endotoxin. However, recent work shows that synthetic lipid X can be contaminated with small amounts of N,O-acylated disaccharide-1-phosphate (H. Aschauer, A. Grob, J. Hildebrandt, E. Schuetze, and P. Steutz, J. Biol. Chem. 265:9159-9164, 1990). Because the impurities themselves exhibit immunostimulatory properties, it was necessary to establish whether chemically pure synthetic lipid X exhibits any of the endotoxinlike biological activities previously attributed to the native compound extracted from the Escherichia coli MN7 mutant. In the present study, two batches of synthetic lipid X were used: batch A contained the contaminating disaccharide, and batch B was pure lipid X. Batch A, previously believed to be pure on the basis of spectroscopic and microanalysis data, induced murine peritoneal macrophages to secrete tumor necrosis factor, interleukin-1, and prostaglandin E2 at a minimal dose of 10 micrograms/ml in vitro. Batch B, further purified by Sephadex LH 20 chromatography, was found virtually inactive in these in vitro assays. Furthermore, batch A was pyrogenic in rabbits at a dose of 0.05 mg/kg, whereas batch B was not pyrogenic at doses of up to greater than or equal to 2 mg/kg. However, both batches were equally tolerated by galactosamine-loaded mice at doses of up to 100 mg/kg. Surprisingly, while only batch A protected neutropenic mice against lethal infection with Pseudomonas aeruginosa (50% effective dose, 12.4 mg/kg), both batches were equally protective against infection with herpes simplex virus type 1 in mice and guinea pigs, even when lipid X was administered therapeutically. Interestingly, both batches of lipid X blocked endotoxin-induced expression of monocyte procoagulant activity and priming of human neutrophils for superoxide anion release. Similarly, both batches protected galactosamine-sensitized mice from otherwise lethal endotoxemia when administered prophylactically or simultaneously with the lipopolysaccharide challenge. Thus, our findings suggest that chemically pure lipid X (batch B) is devoid of the immunostimulatory properties of lipid A or endotoxin. Rather, it behaves as a competitive inhibitor of lipopolysaccharide. We conclude, therefore, that previous studies which attributed immunostimulatory activities to any batch of synthetic lipid X should be interpreted with caution.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Lam C,Hildebrandt J,Schütze E,Rosenwirth B,Proctor RA,Liehl E,Stütz Pdoi
10.1128/IAI.59.7.2351-2358.1991keywords:
subject
Has Abstractpub_date
1991-07-01 00:00:00pages
2351-8issue
7eissn
0019-9567issn
1098-5522journal_volume
59pub_type
杂志文章abstract::Staphylococcal enterotoxins A through D (SEA through SED) and toxic shock syndrome toxin-1 display superantigen properties, i.e., they stimulate a great fraction of T cells expressing certain T-cell receptor V beta sequences. Using a newly established rat model of septic Staphylococcus aureus arthritis, we have recent...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.10.4185-4187.1995
更新日期:1995-10-01 00:00:00
abstract::An impressive change in the epidemiology and severity of invasive group A streptococcal infections occurred in the 1980s, and the incidence of streptococcal toxic shock syndrome cases continues to rise. The reason for the resurgence of severe invasive cases remains a mystery-has there been a change in the pathogen or ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::Ehrlichia chaffeensis is an obligately intracellular gram-negative bacterium and is the etiologic agent of human monocytic ehrlichiosis (HME). Although E. chaffeensis induces the generation of several cytokines and chemokines by leukocytes, E. chaffeensis lacks lipopolysaccharide and peptidoglycan. Bioinfomatic analys...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00056-08
更新日期:2008-08-01 00:00:00
abstract::This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccin...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.74.5.2734-2741.2006
更新日期:2006-05-01 00:00:00
abstract::Strain superinfection occurs when a second pathogen strain infects a host already carrying a primary strain. Anaplasma marginale superinfection occurs when the second strain carries a variant repertoire different from that of the primary strain, and the epidemiologic consequences depend on the relative efficiencies of...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01518-08
更新日期:2009-04-01 00:00:00
abstract::Escherichia coli is a major cause of enteric/diarrheal diseases, urinary tract infections, and sepsis. E. coli K1 is the leading gram-negative organism causing neonatal meningitis, but the microbial basis of E. coli K1 meningitis is incompletely understood. Here we employed comparative genomic hybridization to investi...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.74.4.2196-2206.2006
更新日期:2006-04-01 00:00:00
abstract::Contributions of the alternative sigma factor sigmaB to Listeria monocytogenes infection were investigated using strains bearing null mutations in sigB, prfA, or inlA or in selected inlA or prfA promoter regions. The DeltaP4inlA strain, which has a deletion in the sigmaB-dependent P4inlA promoter, and the DeltasigB st...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.74.2.876-886.2006
更新日期:2006-02-01 00:00:00
abstract::The zoopathogenic fungus Histoplasma capsulatum requires iron for growth. Intracellular growth of the fungus within mouse peritoneal macrophages is inhibited by recombinant murine gamma interferon (IFN-gamma). Such treatment of mouse peritoneal macrophages induces a marked downshift in transferrin receptors. We tested...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.7.2274-2278.1991
更新日期:1991-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.51.2.529-535.1986
更新日期:1986-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.2.3.326-339.1970
更新日期:1970-09-01 00:00:00
abstract::Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori is the major cause of acute and chronic gastroduodenal pathologies in humans. Duodenal ulcer formation strongly correlates with the expression of an antigen (CagA) that is usually coeexpressed with the vacuolating cytotoxin (VacA), a pro...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.1.94-98.1995
更新日期:1995-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.10.4301-4308.1992
更新日期:1992-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.70.2.771-778.2002
更新日期:2002-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.50.1.77-81.1985
更新日期:1985-10-01 00:00:00
abstract::Human monocytic ehrlichiosis (HME) is caused by a tick-borne obligate intracellular pathogen of the order Rickettsiales. HME disease can range from mild to a fatal, toxic shock-like syndrome, yet the mechanisms regulating pathogenesis are not well understood. We define a central role for type I interferons (alpha inte...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01564-13
更新日期:2014-04-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01142-10
更新日期:2011-06-01 00:00:00
abstract::A 46-kDa hemolytic protein, referred to as cystalysin, from Treponema denticola ATCC 35404 was overexpressed in Escherichia coli LC-67. Both the native and recombinant 46-kDa proteins were purified to homogeneity. Both proteins expressed identical biological and functional characteristics. In addition to its biologica...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.65.8.3231-3238.1997
更新日期:1997-08-01 00:00:00
abstract::Acquisition of genomic elements by horizontal gene transfer represents an important mechanism in the evolution of bacterial species. Pathogenicity islands are a subset of horizontally acquired elements present in various pathogens. These elements are frequently located adjacent to tRNA genes. We performed a comparativ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.70.5.2351-2360.2002
更新日期:2002-05-01 00:00:00
abstract::The purpose of this study was to localize antigenic regions on the flagellin protein of Campylobacter jejuni 81116. This strain has two flagellin genes, flaA and flaB, which are 95% identical; only flaA seems to be expressed in motile C. jejuni 81116 cells. Fragments of flaA and flaB were cloned in the bacterial expre...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.3.1100-1105.1991
更新日期:1991-03-01 00:00:00
abstract::The role of gamma-delta T cells in host resistance to Chlamydia trachomatis was characterized by using a murine model of pneumonia caused by the mouse pneumonitis agent (MoPn), murine C. trachomatis. At days 3 and 7 after infection, gamma-delta T-cell-deficient knockout mice had significantly higher levels of MoPn in ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.9.3916-3919.1996
更新日期:1996-09-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.24.3.617-627.1979
更新日期:1979-06-01 00:00:00
abstract::Mannan (MAN) extracted from Candida albicans 20A was investigated for its potential as an antigen in the detection of cell-mediated immunity (CMI) in vivo and in vitro and for its ability to modulate CMI when administered intravenously (i.v.). CBA/J mice were either immunized as adults by the cutaneous inoculation of ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.57.3.693-700.1989
更新日期:1989-03-01 00:00:00
abstract::Vibrio parahaemolyticus is a gram-negative marine bacterium. A limited population of the organisms causes acute gastroenteritis in humans. Almost all of the clinical V. parahaemolyticus isolates exhibit beta-type hemolysis on Wagatsuma agar, known as the Kanagawa phenomenon (KP). KP is induced by the thermostable dire...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01535-07
更新日期:2008-03-01 00:00:00
abstract::Actinobacillus actinomycetemcomitans SUNY 465, the invasion prototype strain, enters epithelial cells by an actin-dependent mechanism, escapes from the host cell vacuole, and spreads intracellularly and to adjacent epithelial cells via intercellular protrusions. Internalized organisms also egress from host cells into ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::The adsorption of (3)H-labeled Streptococcus mutans 6715 cells to disks of hydroxyapatite (HA) was studied. The number of streptococci that adsorbed was logarithmically related to the concentration of cells available up to at least 2 x 10(8) per ml; equilibrium occurred within 45 min. Assay reliability was verified by...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.18.2.514-523.1977
更新日期:1977-11-01 00:00:00
abstract::The chlamydial inclusion occupies a unique niche within the eukaryotic cell that does not interact with endocytic compartments but instead is fusogenic with a subset of sphingomyelin-containing exocytic vesicles. The Chlamydia trachomatis inclusion acquires these distinctive properties by as early as 2 h postinfection...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.71.2.973-984.2003
更新日期:2003-02-01 00:00:00
abstract::Alternate modalities for the treatment of Mycobacterium tuberculosis are needed due to the rise in numbers of immunosuppressed individuals at risk for serious disease and the increasing prevalence of multidrug-resistant isolates. Interleukin-12 (IL-12) has been shown to improve immune responses against M. tuberculosis...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.72.5.2976-2988.2004
更新日期:2004-05-01 00:00:00
abstract::Natural killer (NK) cells are considered to be key players in the early innate responses to protozoan infections, primarily indirectly by producing gamma interferon (IFN-gamma) in response to cytokines, like interleukin 12 (IL-12). We demonstrate that live, as well as heat-inactivated, tachyzoites of Neospora caninum,...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.74.2.953-960.2006
更新日期:2006-02-01 00:00:00
abstract::One major outer membrane protein (P1) of Haemophilus influenzae type b (Hib), with an apparent molecular weight of 34,000 (34K) as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), has been shown to be heat modifiable. After heating at 100 degrees C for 5 min in 2% SDS, the P1 protein...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.12.2993-3000.1987
更新日期:1987-12-01 00:00:00
abstract::Burkholderia pseudomallei is a CDC tier 1 select agent that causes melioidosis, a severe disease in humans and animals. Persistent infections are common, and there is currently no vaccine available. Lipopolysaccharide (LPS) is a potential vaccine candidate. B. pseudomallei expresses three serologically distinct LPS ty...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.02785-14
更新日期:2015-05-01 00:00:00