Journal of endotoxin research最新文献

{"title":"Mechanisms of endotoxin neutralization by synthetic cationic compounds.","authors":"Jörg Andrä,&nbsp;Thomas Gutsmann,&nbsp;Patrick Garidel,&nbsp;Klaus Brandenburg","doi":"10.1179/096805106X118852","DOIUrl":"https://doi.org/10.1179/096805106X118852","url":null,"abstract":"<p><p>A basic challenge in the treatment of septic patients in critical care units is the release of bacterial pathogenicity factors such as lipopolysaccharide (LPS, endotoxin) from the cell envelope of Gram-negative bacteria due to killing by antibiotics. LPS aggregates may interact with serum and membrane proteins such as LBP (lipopolysaccharide-binding protein) and CD14 leading to the observed strong reaction of the immune system. Thus, an effective treatment of patients infected by Gram-negative bacteria must comprise beside bacterial killing the neutralization of endotoxins. Here, data are summarized for synthetic compounds indicating the stepwise development to very effective LPS-neutralizing agents. These data include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, and cathelicidins or based on LPS sequestering polyamines. Many of these compounds could be shown to act not only in vitro, but also in vivo (e.g. in animal models of sepsis), and might be useful in future clinical trials and in sepsis therapy.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 5","pages":"261-77"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X118852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26326102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination and de-ubiquitination: role in regulation of signaling by Toll-like receptors.","authors":"Emily L Lowe,&nbsp;Terence M Doherty,&nbsp;Hisae Karahashi,&nbsp;Moshe Arditi","doi":"10.1179/096805106X118915","DOIUrl":"https://doi.org/10.1179/096805106X118915","url":null,"abstract":"<p><p>Signaling by Toll-like receptors (TLRs) has attracted accelerating attention over the past decade because of the central role of TLR signaling in both innate and adaptive immunity. In addition, TLR signaling is now increasingly implicated in a remarkably wide range of diseases that are either caused, or accompanied, by dysregulated inflammation. Much has been learned about the basic signaling framework and participants, as well as how signaling is turned off and fine-tuned. Here, we summarize key aspects of TLR signaling, focusing on interaction with the anti-inflammatory TGF-beta signaling network. We propose that ubiquitination and de-ubiquitination of TLR pathway components may be a mechanism by which predominantly anti-inflammatory input is integrated into the host response to fine-tune inflammation in accordance with the needs of host defenses.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 6","pages":"337-45"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X118915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26513918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Origin of monocytes and their differentiation to macrophages and dendritic cells.","authors":"Suresh Kumar,&nbsp;Robert Jack","doi":"10.1179/096805106X118861","DOIUrl":"https://doi.org/10.1179/096805106X118861","url":null,"abstract":"<p><p>Activation of the immune system requires that the presence of an incipient infection first be detected. This essential step is carried out by tissue macrophages, which alert innate immunity, and by dendritic cells whih alert the adaptive immune system. Both of these sentinel cell types are derived from circulating precursors known as blood monocytes. Here we briefly review current work which has recently expanded our understanding of the origin of blood monocytes and of the factors governing their further differentiation into tissue sentinels.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 5","pages":"278-84"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X118861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26326078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural features and structural variability of the lipopolysaccharide of Yersinia pestis, the cause of plague.","authors":"Yuriy A Knirel,&nbsp;Svetlana V Dentovskaya,&nbsp;Sof'ya N Senchenkova,&nbsp;Rima Z Shaikhutdinova,&nbsp;Nina A Kocharova,&nbsp;Andrey P Anisimov","doi":"10.1179/096805105X67283","DOIUrl":"https://doi.org/10.1179/096805105X67283","url":null,"abstract":"<p><p>Data on the structure and temperature-dependent variations of the lipopolysaccharide (LPS) of Yersinia pestis are summarized and compared with data of other enteric bacteria, including other Yersinia spp. A correlation between the LPS structure and properties of the LPS and bacterial cultures as well as the LPS biosynthesis control are briefly discussed.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 1","pages":"3-9"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805105X67283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25806968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-atherogenic properties of lipopolysaccharide from the periodontal pathogen Actinobacillus actinomycetemcomitans.","authors":"Laura Lakio,&nbsp;Markku Lehto,&nbsp;Anita M Tuomainen,&nbsp;Matti Jauhiainen,&nbsp;Ernst Malle,&nbsp;Sirkka Asikainen,&nbsp;Pirkko J Pussinen","doi":"10.1179/096805106X89099","DOIUrl":"https://doi.org/10.1179/096805106X89099","url":null,"abstract":"An association between cardiovascular and periodontal disease may be due to lipopolysaccharide (LPS)-promoted release of inflammatory mediators, adverse alterations of the lipoprotein profile, and an imbalance in cholesterol homeostasis. Since periodontopathogenic potential differs between serotypes of a major periodontal pathogen, Actinobacillus actinomycetemcomitans, we studied the pro-atherogenic properties of LPS preparations from serotypes b and d strains on macrophages (RAW 264.7). A. actinomycetemcomitans LPS preparations induced a time-dependent release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). LPS induced foam cell formation and cholesteryl ester accumulation from native low density lipoprotein in the following order: A. actinomycetemcomitans strains JP2 (serotype b) > Y4 (serotype b) > IDH781 (serotype d). mRNA expression levels of scavenger receptor class B, type-I, and ATP-binding cassette transporter-1, receptors mediating cholesterol efflux from macrophages, were decreased by LPS preparations. The results suggest that the pro-atherogenic potential of A. actinomycetemcomitans LPS may depend on the infecting strain and correlate with the periodontopathogenic potential of the pathogen.","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 1","pages":"57-64"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X89099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25808076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide-induced proliferation and adhesion of U937 cells to endothelial cells involves barium chloride sensitive hyperpolarization.","authors":"Ali Erdogan,&nbsp;Christian Alexander Schaefer,&nbsp;Astrid Kerstin Most,&nbsp;Martina Barbara Schaefer,&nbsp;Konstantin Mayer,&nbsp;Harald Tillmanns,&nbsp;Christoph Ruediger Wolfram Kuhlmann","doi":"10.1179/096805106X102228","DOIUrl":"https://doi.org/10.1179/096805106X102228","url":null,"abstract":"<p><p>The adhesion of monocytes to the endothelium and their proliferation in the subendothelial space play an important role in atherosclerosis. Since the proliferation and migration of cells are influenced by the activity of ion channels, the aim of this study was to examine whether barium chloride (Ba(2+))-sensitive potassium channels (K(iCa)) are involved in lipopolysaccharide (LPS)-induced proliferation of monocytic U937 cells, and in the adhesion of these cells to endothelial cells. The adhesion of LPS-stimulated U937 cells to endothelial cells reached a maximum at a concentration of 5 microg/ml. This effect of LPS was completely abolished in the presence of Ba(2+) (100 micromol/l). In addition, LPS-induced proliferation was significantly reduced by Ba(2+) (control, 100%; LPS 5 microg/ml, 175%; LPS + Ba(2+) 100 micromol/l, 136%; n = 12, P < 0.05). To examine whether K(iCa) are activated by LPS, changes of U937 membrane potential were determined. LPS (5 microg/ml) caused a hyperpolarization of U937 cells indicating a flux of K(+) ions out of the cells. This effect was completely blocked by Ba(2+) (100 micromol/l). In conclusion, we demonstrate that LPS activates K(iCa) in U937 cells, which is responsible for LPS-induced adhesion of these cells to endothelial cells, and to the proliferation of U937 cells.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 4","pages":"224-30"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X102228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26295766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA and RNA autoantigens as autoadjuvants.","authors":"Liliana Busconi,&nbsp;Christina M Lau,&nbsp;Abigail S Tabor,&nbsp;Melissa B Uccellini,&nbsp;Zachary Ruhe,&nbsp;Shizuo Akira,&nbsp;Gregory A Viglianti,&nbsp;Ian R Rifkin,&nbsp;Ann Marshak-Rothstein","doi":"10.1179/096805106X118816","DOIUrl":"https://doi.org/10.1179/096805106X118816","url":null,"abstract":"<p><p>AM14 B cells are a prototype for those low affinity autoreactive B cells that routinely mature as naïve cells in peripheral lymphoid tissues. These cells express a transgene-encoded receptor specific for IgG2a and can be effectively activated by immune complexes that incorporate either mammalian DNA or mammalian RNA that has been released from dead or dying cells. Activation depends on the ability of the B-cell receptor to deliver antigen to an internal vesicular compartment containing either Toll-like receptor-9 (TLR9) or TLR7. Since TLR9 and TLR7 are thought to recognize microbial DNA and RNA preferentially, it is important to determine under what conditions mammalian DNA and RNA become effective TLR ligands, and whether the determining factor is delivery or structure. This issue has been addressed by using IgG2a mAbs to deliver immune complexes preloaded with defined fragments of DNA or RNA, or by using modified ODNs/ORNs. The data demonstrate that only certain nucleic acid sequences or structures can induce autoreactive B-cell proliferation, even when delivery to the appropriate TLR compartment is facilitated by uptake through the B-cell receptor (BCR).</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 6","pages":"379-84"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X118816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26514374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GM-CSF priming of human monocytes is dependent on ERK1/2 activation.","authors":"Sven Lendemans,&nbsp;Meenakshi Rani,&nbsp;Christian Selbach,&nbsp;Ernst Kreuzfelder,&nbsp;Fritz Ulrich Schade,&nbsp;Sascha Flohé","doi":"10.1179/096805106X89107","DOIUrl":"https://doi.org/10.1179/096805106X89107","url":null,"abstract":"<p><p>The ability to augment monocyte functions such as TNF-alpha-producing capacities confers a high immunostimulating potential to GM-CSF. In the present investigation, the mechanism of the GMCSF-mediated enhancement of monocyte cytokine production was analysed with regard to the involvement of intracellular signalling pathways. GM-CSF primes human monocytes dose- and time-dependently for enhanced LPS-stimulated TNF-alpha synthesis. Pre-incubation with 10 ng/ml GM-CSF for 6 h before LPS stimulation (10 ng/ml) caused a 3.4 +/- 1.9-fold increase in TNF-alpha release compared to unprimed controls. This was associated with increased phosphorylation of IkappaBalpha and elevated nuclear levels of the NF-kappaB components p50 and p65 and NF-kappaB binding to DNA. LPS-induced AP-1 binding to DNA was also enhanced in GM-CSF-pre-incubated cells. GMCSF treatment also caused a slight increase in TLR4 expression on monocytes while CD14 expression remained unchanged. GM-CSF-priming was unaffected by inhibitors of p38 MAPK (SB203580) and lipoxygenase (NDGA). In contrast, the broad-spectrum tyrosine kinase inhibitor genistein and the MEK-1 inhibitor (PD98059) abrogated GM-CSF priming of TNF-alpha release and activation of both NF-kappaB and AP-1. It is concluded that a tyrosine kinase of the GM-CSF-triggered ERK1/2 pathway augments the LPS-induced NF-kappaB and AP-1 activation.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 1","pages":"10-20"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X89107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25806969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compartmentalization of the inflammatory response in sepsis and SIRS.","authors":"Jean-Marc Cavaillon,&nbsp;Djillali Annane","doi":"10.1179/096805106X102246","DOIUrl":"https://doi.org/10.1179/096805106X102246","url":null,"abstract":"<p><p>Sepsis and systemic inflammatory response syndrome (SIRS) are associated with an exacerbated production of both pro- and anti-inflammatory mediators that are mainly produced within tissues. Although a systemic process, the pathophysiological events differ from organ to organ, and from organ to peripheral blood, leading to the concept of compartmentalization. The nature of the insult (e.g. burn, hemorrhage, trauma, peritonitis), the cellular composition of each compartment (e.g. nature of phagocytes, nature of endothelial cells), and its micro-environment (e.g. local presence of granulocyte-macrophage colony stimulating factor [GM-CSF] in the lungs, low levels of arginine in the liver, release of endotoxin from the gut), and leukocyte recruitment, have a great influence on local inflammation and on tissue injury. High levels of pro-inflammatory mediators (e.g. interleukin-1 [IL-1], tumor necrosis factor [TNF], gamma interferon [IFN-gamma], high mobility group protein-1 [HMGB1], macrophage migration inhibitory factor [MIF]) produced locally and released into the blood stream initiate remote organ injury as a consequence of an organ cross-talk. The inflammatory response within the tissues is greatly influenced by the local delivery of neuromediators by the cholinergic and sympathetic neurons. Acetylcholine and epinephrine contribute with IL-10 and other mediators to the anti-inflammatory compensatory response initiated to dampen the inflammatory process. Unfortunately, this regulatory response leads to an altered immune status of leukocytes that can increase the susceptibility to further infection. Again, the nature of the insult, the nature of the leukocytes, the presence of circulating microbial components, and the nature of the triggering agent employed to trigger cells, greatly influence the immune status of the leukocytes that may differ from one compartment to another. While anti-inflammatory mediators predominate within the blood stream to avoid igniting new inflammatory foci, their presence within tissues may not always be sufficient to prevent the initiation of a deleterious inflammatory response in the different compartments.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 3","pages":"151-70"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1179/096805106X102246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26041355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of incremental inhaled lipopolysaccharide challenge in humans.","authors":"John S Sundy,&nbsp;William A Wood,&nbsp;Janet L Watt,&nbsp;Joel N Kline,&nbsp;David A Schwartz","doi":"10.1177/09680519060120020701","DOIUrl":"https://doi.org/10.1177/09680519060120020701","url":null,"abstract":"<p><strong>Background: </strong>Inhalation of environmental endotoxin is important in the pathogenesis of asthma and other environmental airway diseases. Inhaled airway challenge using lipopolysaccharide in humans has been performed for over 20 years to assess the airway response to endotoxin. However, there are no published data on the short-term safety of endotoxin inhalation protocols.</p><p><strong>Objective: </strong>To characterize the safety and tolerability of incremental inhaled lipopolysaccharide challenge in humans.</p><p><strong>Patients and methods: </strong>We performed a retrospective analysis of data obtained from 119 subjects who underwent inhaled challenge with up to 41.5 mug of lipopolysaccharide. We measured pulmonary function, temperature, mean arterial pressure, heart rate, and systemic symptoms for 3 h after challenge.</p><p><strong>Results: </strong>Fever occurred in 30% of subjects and was associated with a higher cumulative dose of lipopolysaccharide. Reduced mean arterial pressure occurred in 21% of subjects and was dose-related. There was no association between fever or decreased mean arterial pressure and airway responsiveness to inhaled lipopolysaccharide. Common symptoms reported by subjects included: chills (64%), malaise (56%), cough (56%), chest tightness (49%), headache (43%), and myalgias (27%). None of the subjects experienced delayed discharge or a serious adverse event.</p><p><strong>Conclusions: </strong>Inhaled lipopolysaccharide causes dose-related systemic responses that include fever, reduced blood pressure, and constitutional symptoms that are not associated with the airway response to inhaled lipopolysaccharide. Systemic responses to inhaled lipopolysaccharide should be expected and subjects undergoing inhaled lipopolysaccharide challenge in the research setting should be carefully monitored for non-pulmonary adverse events for several hours after challenge.</p>","PeriodicalId":80292,"journal":{"name":"Journal of endotoxin research","volume":"12 2","pages":"113-9"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/09680519060120020701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26016531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}