Shiga Toxin and Lipopolysaccharide Induce Platelet-Leukocyte Aggregates and Tissue Factor Release, a Thrombotic Mechanism in Hemolytic Uremic Syndrome

BACKGROUND: Aggregates formed between leukocytes and platelets in the circulation lead to release of tissue factor (TF)-bearing microparticles contributing to a prothrombotic state. As enterohemorrhagic Escherichia coli (EHEC) may cause hemolytic uremic syndrome (HUS), in which microthrombi cause tissue damage, this study investigated whether the interaction between blood cells and EHEC virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS) led to release of TF. METHODOLOGY/PRINCIPAL FINDINGS: The interaction between Stx or LPS and blood cells induced platelet-leukocyte aggregate formation and tissue factor (TF) release, as detected by flow cytometry in whole blood. O157LPS was more potent than other LPS serotypes. Aggregates formed mainly between monocytes and platelets and less so between neutrophils and platelets. Stimulated blood cells in complex expressed activation markers, and microparticles were released. Microparticles originated mainly from platelets and monocytes and expressed TF. TF-expressing microparticles, and functional TF in plasma, increased when blood cells were simultaneously exposed to the EHEC virulence factors and high shear stress. Stx and LPS in combination had a more pronounced effect on platelet-monocyte aggregate formation, and TF expression on these aggregates, than each virulence factor alone. Whole blood and plasma from HUS patients (n = 4) were analyzed. All patients had an increase in leukocyte-platelet aggregates, mainly between monocytes and platelets, on which TF was expressed during the acute phase of disease. Patients also exhibited an increase in microparticles, mainly originating from platelets and monocytes, bearing surface-bound TF, and functional TF was detected in their plasma. Blood cell aggregates, microparticles, and TF decreased upon recovery. CONCLUSIONS/SIGNIFICANCE: By triggering TF release in the circulation, Stx and LPS can induce a prothrombotic state contributing to the pathogenesis of HUS

Lipopolysaccharide Renders Transgenic Mice Expressing Human Serum Amyloid P Component Sensitive to Shiga Toxin 2

Transgenic C57BL/6 mice expressing human serum amyloid P component (HuSAP) are resistant to Shiga toxin 2 (Stx2) at dosages that are lethal in HuSAP-negative wild-type mice. However, it is well established that Stx2 initiates extra-intestinal complications such as the haemolytic-uremic syndrome despite the presence of HuSAP in human sera. We now demonstrate that co-administering purified Escherichia coli O55 lipopolysaccharide (LPS), at a dosage of 300 ng/g body weight, to HuSAP-transgenic mice increases their susceptibility to the lethal effects of Stx2. The enhanced susceptibility to Stx2 correlated with an increased expression of genes encoding the pro-inflammatory cytokine TNFα and chemokines of the CXC and CC families in the kidneys of LPS-treated mice, 48 hours after the Stx2/LPS challenge. Co-administering the glucocorticoid dexamethasone, but not the LPS neutralizing cationic peptide LL-37, protected LPS-sensitized HuSAP-transgenic mice from lethal doses of Stx2. Dexamethasone protection was specifically associated with decreased expression of the same inflammatory mediators (CXC and CC-type chemokines and TNFα) linked to enhanced susceptibility caused by LPS. The studies reveal further details about the complex cascade of host-related events that are initiated by Stx2 as well as establish a new animal model system in which to investigate strategies for diminishing serious Stx2-mediated complications in humans infected with enterohemorrhagic E. coli strains

タンシキン ヒラタケ ノ マンガン ペルオキシダーゼ アイソザイム ニ カンスル ケンキュウ : トクイテキ イデンシ ハツゲン ト ポリマー ブンカイ ニ オケル キノウ トクセイ

京都大学0048新制・課程博士博士(農学)甲第10910号農博第1416号新制||農||891(附属図書館)学位論文||H16||N3921(農学部図書室)UT51-2004-G757京都大学大学院農学研究科応用生命科学専攻(主査)教授 渡邊 隆司, 教授 島田 幹夫, 教授 江崎 信芳学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDA

<Preliminary>Studies on the Production of Manganese Peroxidase by a White-rot Fungus Pleurotus ostreatus

この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました

Packaging design: a study case of european grape with seeds

A uva é uma das frutas in natura mais consumidas no Brasil e no mundo. A sua fragilidade e perecibilidade exigem embalagens adequadas, que além de proteger a uva sirvam para a sua exposição e promoção. Foram entrevistados 33 atacadistas responsáveis por 80% do volume da uva européia com semente, comercializada na CEAGESP - Companhia de Entreposto Armazéns Gerais do Estado de São Paulo. A primeira entrevista levantou a percepção das características e da importância da embalagem pelos atacadistas. A segunda entrevista tratou da escolha pelos atacadistas das características da embalagem ideal e permitiu o design de quatro modelos de embalagem. As características comuns aos quatros modelo da embalagem ideal são: caixa de papelão ondulado, aberta, com abas nas laterais, reforço nas quinas, impermeabilização, cor de fundo branca, duas cores de cobertura (vermelho e verde), com ilustração, peso líquido de 5 kg, altura de 14 cm, largura de 30 cm e comprimento de 40 cm. As características que as diferenciam são o número de furos de ventilação dois ou três e a localização das travas - na testeira ou na lateral.The grape is one of the most consumed fresh fruit in Brazil and worldwide. Because Its fragility and perishability, it requires proper packaging, which also serves to protect, expose and promote. We have interviewed 33 wholesalers responsible for 80% of the volume of seeded european grape at Sao Paulo Terminal Market of CEAGESP. The first interview has evaluated the characteristics and importance of packaging perception by wholesalers. At the second interview the wholesalers have chosen the package ideal characteristies for the seeded european grapes and they have concluded for four different package models. The common characteristics of the ideal packaging are: corrugated box, open box, with tabs on the sides, reinforcing the corners, waterproofing, white background, two-color cover (red and green), with illustration, weight 5 kg, height 14 cm, width 30 cm and length 40 cm. The characteristics that differentiate are the number of ventilation holes, two or three and the place of locks - on the frontlet or the side