Fractalkine is not a major chemoattractant for the migration of neutrophils across microvascular endothelium

Fractalkine is not a major chemoattractant for the migration of neutrophils across microvascular endothelium
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DOI:
10.1046/j.1365-3083.2003.01298.x
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发表时间:
2003-08-01
影响因子:
3.7
通讯作者:
Yard, BA
Yard, BA
中科院分区:
医学4区
文献类型:
--
作者:
Beck, GC;Ludwig, F;Yard, BA

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脓毒症期间的炎症反应由白细胞募集到发炎组织中决定。趋化因子和粘附分子都被认为参与了这一过程。由于fractalkine作为具有细胞粘附特性的跨膜蛋白和可溶性趋化因子存在,因此本研究进行了研究,以研究微血管和大血管内皮细胞产生的fractalkine在中性粒细胞募集中的作用。肺微血管内皮细胞(LMVECs)刺激脂多糖,肿瘤坏死因子-α或白细胞介素-1(IL-1)产生更多的fractalkine相比,大血管的人脐静脉内皮细胞(HUVECs)。不同器官的微血管内皮细胞之间无差异。与HUVEC相比,刺激的LMVEC上清液中的趋化活性显著增强。虽然重组fractalkine诱导中性粒细胞的迁移,IL-8和单核细胞趋化蛋白-1被认为是更严格的要求。体内fractalkine在脓毒症肺和肾中强烈上调。我们的数据表明,fractalkine生产本身并不能解释脓毒症患者肺部炎症的偏好。
Inflammatory responses during sepsis are determined by leucocyte recruitment into inflamed tissues. Both chemokines and adhesion molecules are believed to be involved in this process. As fractalkine exists as transmembrane protein with cell adhesion properties and as soluble chemotactic factor, the present study was conducted to study the role of fractalkine, produced by microvascular and macrovascular endothelial cells, in neutrophil recruitment. Lung microvascular endothelial cells (LMVECs) stimulated with lipopolysaccharide, tumour necrosis factor-alpha or interleukin-1 (IL-1) produced much more fractalkine compared with the macrovascular human umbilical vein endothelial cells (HUVECs). No differences were found between microvascular endothelial cells of different organs. Chemotactic activity in supernatants was significantly stronger in stimulated LMVEC when compared with HUVEC. Although recombinant fractalkine induced migration of neutrophils, IL-8 and monocyte chemoattractant protein-1 were found to be more strictly required. In vivo fractalkine was strongly upregulated in septic lung and kidney. Our data suggest that fractalkine production per se does not explain the preference for inflammation in the lung of septic patients.