The Molecular Mechanism of Late Phase Adverse Reaction of Contrast Media

造影剂晚期不良反应的分子机制

• 批准号: 10671772
• 负责人: NOIKURA Takenori
• 金额: $ 2.05万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671772/
• 关键词: Adverse reaction; Late phase; Endothelial cells; P-selectin; NF-kappa B; nitruc oxide; iNOS; Contrast media; P-selectin、ICAM-1; NF-κBの活性化; 誘導型NO合成酵素(iNOS); NOの生産; P-selectin,ICAM-1; 誘導型NO合成酵素(NOS); NOの産生

Endothelial Selectins, such as P-selectin and E-selectin, mediate cell adhesion of monocytes or neutrophils to activated endothelial cells. Previously we reported an upregulated expression of inflammatory cytokines by P-selectin-mediated neutrophil attachment to activated endothelium stimulated by contrast media.We examined the effect of endothelial selectins on the expression of inflammatory cytokines, nitric oxide production and on the activation of NF-kappa B. We found that the soluble forms of P-selectin and E-selectin as well as the monocyte-endothelial interaction induced upregulated the expression of inflammatory cytokines and the production of nitric oxide. These expression of inflammatory cytokines involved the activation of NF-kappa B pathway by the reactive oxygen intermediate (ROI). P-selectin specifically induced β2-integrin (CD11b)-mediated sticky adhesion of monocytes, via ROI generation. Then P-selectin-mediated rapid activation of NF-kappa B, which was augmented by following with β2-integrin (CD11b)-induced sticky adhesion. The binding of endothelial selectins to monocytes in the area of vascular activation by contrast media is considered to be a component of the mechanism that initiates thrombosis and hypotension after the administration of contrast media.

内皮选择素，如p -选择素和e -选择素，介导单核细胞或中性粒细胞与活化的内皮细胞的粘附。先前我们报道了在造影剂刺激下，p选择素介导的中性粒细胞附着在活化的内皮细胞上，炎症细胞因子的表达上调。我们研究了内皮选择素对炎症细胞因子的表达、一氧化氮的产生和NF-kappa b的激活的影响。我们发现p选择素和e选择素的可溶性形式以及单核细胞内皮相互作用诱导的炎症细胞因子的表达和一氧化氮的产生上调。这些炎症细胞因子的表达涉及到NF-kappa B途径被活性氧中间体（ROI）激活。p -选择素通过ROI生成特异性诱导β2-整合素（CD11b）介导的单核细胞黏附。然后p选择素介导NF-kappa B的快速激活，随后通过β2-整合素（CD11b）诱导的粘性粘附增强NF-kappa B的激活。造影剂激活血管区内皮选择素与单核细胞的结合被认为是造影剂使用后引发血栓形成和低血压的机制的一个组成部分。

项目成果

Matsushita Y., Maruyama I: "A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared high thrombomodulin expressing clone-thrombomodulin as a possible candidate for an adhesio

Matsushita Y.，Maruyama I：“与高血栓调节蛋白表达的克隆血栓调节蛋白相比，具有低血栓调节蛋白表达的亚克隆人食管鳞状细胞癌细胞系显示出更高的侵袭性，作为粘附的可能候选者

Maruyama I: Thromb Hoemost. 82. 718-721 (1999)

丸山一世：血栓霍莫斯特。

Nakata M., Maruyama, I: "DX9065X, an Xu inhibitor, inhibits prothrombin-induced A549 lung adenocarcinoma cell proliferation"Cancer Lett. 122. 127-133 (1998)

Nakata M.，Maruyama，I：“DX9065X，一种 Xu 抑制剂，抑制凝血酶原诱导的 A549 肺腺癌细胞增殖”Cancer Lett。

Maruyama.I: "Recombinant thrombomodulin and activated protein C in the treatment of desseninated intravascular."Thromb Haemost.. 82. 718-721 (1999)

Maruyama.I：“重组血栓调节蛋白和活化蛋白 C 治疗血管内脱髓细胞。”Thromb Haemost.. 82. 718-721 (1999)

Matsushita.Y,Maruyama.I,: "A subcloned human esophageal sqaumous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin-expressing clone-thrombomodulin as a possible candidate for an a

Matsushita.Y，Maruyama.I，：“与高血栓调节蛋白表达的克隆血栓调节蛋白相比，具有低血栓调节蛋白表达的亚克隆人食管鳞状细胞癌细胞系显示出更高的侵袭性，作为一种可能的候选者