The Molecular Mechanism of Late Phase Adverse Reaction 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激活的内皮细胞的黏附。在此之前，我们报道了P-选择素介导的中性粒细胞与对比剂刺激激活的内皮细胞黏附上调炎性细胞因子的表达。我们检测了内皮选择素对炎性细胞因子的表达、一氧化氮的产生以及对核因子-kappaB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与内皮的相互作用上调了炎性细胞因子的表达和一氧化氮的产生。这些炎性细胞因子的表达参与了活性氧中间体(ROI)对核因子-kappaB通路的激活。P-选择素通过感兴趣区的产生，特异性地诱导β-2-整合素(CD11b)介导的单核细胞黏附。然后P-选择素介导的核因子-kappaB的快速激活，再加上β2-整合素(CD11b)诱导的粘附性增强。造影剂使血管激活区内皮细胞选择素与单核细胞结合，被认为是造影剂引起血栓形成和低血压的机制之一。

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.