Limitation of Polymyxin B on Suppression of Endotoxin Shock Induced by Salmonella Infection in Mice

Morita, Hiroyuki; Hasunuma, Ryoichi; Kawaguchi, Kiichiro; Adachi, Yoshiyuki; Tanaka, Shigenori; Kumazawa, Yoshio

doi:10.1248/bpb.27.1840

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…Blockage of CD14 and LPS-binding protein with antibodies or experiments using CD14 knockout mice resulted in prevention of LPS-induced shock (12,13). However, limitation of polymyxin B and anti-LPS antibodies have been shown to be relatively ineffective at combating the morbidity caused by bacterial infection (9). Sialic acids (SAs) are a family of 9-carbon carboxylated monosaccharides typically located at the termini of mammalian cell surface sugar chains on both glycoproteins and glycolipids (14).…”

Section: Introductionmentioning

confidence: 99%

Sialic Acid Reduces Acute Endotoxemia-Induced Liver Dysfunction in the Rat

Hsu

Yang³

et al. 2009

Shock

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Endotoxemia caused by LPS is a life-threatening and inflammatory condition contributing to multiple organ failure. Viruses or bacteria require sialic acid (SA) for target-cell binding. We suggest that exogenous SA through masking or mediating the binding of LPS to the target cells may attenuate LPS-induced liver dysfunction and cecal ligation and puncture-induced shock. We found that SA can directly scavenge O2-, H2O2, and NO activity by a chemiluminescence analyzer and bind to LPS with high affinity using surface plasmon resonance. Intravenous SA significantly increased plasma SA concentration within 4 h. We then assessed the potential effect of SA on LPS-induced acute endotoxemia in the rat. Intravenous LPS (10-50 mg/kg) dose-dependently increased plasma endotoxin and reactive oxygen species in the blood, bile, and liver and increased plasma alanine aminotransferase and aspartate aminotransferase levels as well as TNF-alpha, monocyte chemoattractant protein 1, tissue inhibitor of metalloproteinase 1, IL-1beta, and IL-6 levels in the rats. Thirty minutes after LPS stimulation, SA decreased LPS-enhanced endotoxin level, oxidative stress, alanine aminotransferase and aspartate aminotransferase levels, and cytokine concentration and ameliorated histopathologic alteration in the liver. We found that SA increased LPS-depressed Mn-superoxide dismutase, CuZn-superoxide dismutase, and heat shock protein 70 and decreased LPS-enhanced iNOS and proapoptotic Bax protein expression in the liver by Western blot. Sialic acid was given after treatment to rats subjected to cecal ligation and puncture, and the hypotensive effect was blunted for 6 h. In conclusion, SA treatment can counteract LPS-enhanced acute endotoxemia and oxidative injury via a direct scavenging reactive oxygen species activity and neutralization potential.

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Section: Introductionmentioning

confidence: 99%

Sialic Acid Reduces Acute Endotoxemia-Induced Liver Dysfunction in the Rat

Hsu

Yang³

et al. 2009

Shock

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“…They hypothesized that the sCD14 produced participates to form a complex with LPS. 34,35) However, in case of CAR-primed mice, the concentration of LPS in the plasma after injection is still unknown. Therefore, further investigations to determine the relationship between the sCD14 level and LPS concentration are required to deduce the death mechanisms of CAR-primed endotoxin shock mice.…”

Section: Discussionmentioning

confidence: 99%

Increment of Plasma Soluble CD14 Level in Carrageenan-Primed Endotoxin Shock Model Mice

Hozumi

Adachi

Murakami

et al. 2006

Biological & Pharmaceutical Bulletin

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Lipopolysaccharide, the constituent of the outer membrane of Gram-negative bacteria is the major pathogen that strongly provokes macrophage activation, and is called "Endotoxin." When a large amount of LPS flows in the blood, monocytes and macrophages are activated and cytokines, for example, Tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6 and nitrogen monoxide (NO), are produced. As a result, the fever, the nettle rash, and the endotoxin shock are caused. Endotoxin shock is still a serious disease, and the mortality is also high. For instance, about 210000 patients a year are die due to endotoxin shock in the United States.1) However, in recent years, the molecules related to LPS recognition have been detected and the mechanism of endotoxin shock has been gradually clarified. Toll-like receptor (TLR) 4, 2-4) MD-2, 5,6) Lipopolysaccharide Binding Protein (LBP) 7) and CD14, 8,9) enumerated as molecules, recognize LPS. First, LBP recognizes to LPS and forms a complex. 7) In the next step, membrane CD14 (mCD14), expressed on the surface of monocytes and macrophages, or soluble CD14 (sCD14), expressed in the blood as the free form, recognizes the complex. The complex is transferred to TLR4/MD-2, and the activation of immunological cells is induced, for instance monocytes and macrophages. 9,10) CD14 is expressed on the surface of monocytes and neutrophils as a 55 kDa GPI-anchored membrane protein (mCD14), and is also present in the serum as a soluble isoform.11) There were some interesting reports about the relationship between soluble CD14 and its physiological role. One is that plasma sCD14 is increased and the expression level of mCD14 is decreased in the onset of sepsis.12) And one of the other reports is that the responsibility to LPS was enhanced remarkably with CD14 existence compared with the condition in the absence of CD14.13) On the other hand, an important role of sCD14 was reported, that it acts in promoting the recognition of LPS by epithelial cells, which do not express mCD14, in vitro. 14) These reports suggest that not only mCD14, but also sCD14, is an important receptor in LPS recognition.There are some reports about increased level of sCD14, especially the sCD14 level in blood in the progress of the pathology, not only sepsis, [15][16][17] but also Kawasaki disease, 18) periodontitis 19) and Alzheimer's disease. 20,21) Therefore, it is thought that CD14 is widely involved in inflammatory disease. To elucidate the relation between the kinetics of the CD14 level and the progress of the pathogenesis may contribute to finding the treatment method.In this research, we compared the kinetics of the sCD14 level in different endotoxin shock models, the iota-carrageenan (CAR)-primed or D-galactosamine (D-galN)-primed model mice. Ogata et al. 22) and our group [23][24][25][26] have been documented that increased TNF-a production might be related to the enhanced lethal toxicity in CAR-primed model mice. 22) Other report describes the mechanisms of the elevated sensitivity to LPS in CAR-primed model m...

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HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

823

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Limitation of Polymyxin B on Suppression of Endotoxin Shock Induced by Salmonella Infection in Mice

Cited by 4 publications

References 26 publications

Sialic Acid Reduces Acute Endotoxemia-Induced Liver Dysfunction in the Rat

Sialic Acid Reduces Acute Endotoxemia-Induced Liver Dysfunction in the Rat

Increment of Plasma Soluble CD14 Level in Carrageenan-Primed Endotoxin Shock Model Mice

HMGB1 in health and disease

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