P-selectin and TNF inhibition reduce venous thrombosis inflammation.
P-selectin and TNF inhibition reduce venous thrombosis inflammation.
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P-选择素和 TNF 抑制可减轻静脉血栓形成炎症。
DOI：
10.1006/jsre.1996.0301
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Greenfield,LJ
中科院分区：
文献类型：
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作者：
Wakefield,TW;Strieter,RM;Downing,LJ;Kadell,AM;Wilke,CA;Burdick,MD;Wrobleski,SK;Phillips,ML;Paulson,JC;Anderson,DC;Greenfield,LJ
静脉血栓形成会引起静脉壁有害的炎症反应。人们发现细胞因子肿瘤坏死因子-α (TNF) 和粘附分子选择素分别在介导炎症细胞刺激和白细胞-内皮细胞粘附中发挥重要作用。本研究评估了 TNF 和 P-选择素在与静脉血栓形成相关的炎症事件中的作用。用单独的中和抗-TNF血清、抗-TNF加抗-P-选择素抗体、单独的抗-P-选择素抗体、对照血清或对照抗-P-选择素抗体对大鼠进行被动免疫。在封闭前以及封闭后第2天和第4天给予抗体或对照血清。闭塞后第 1-6 天和第 13 天处死大鼠进行下腔静脉 (IVC) 壁组织病理学和 TNF 分析。在第2、6和13天发现炎症细胞浸润到静脉壁的程度存在差异。未给予抗TNF抗体的三组的静脉壁中TNF水平升高。第6天的TNF水平与总炎症细胞（r=0.53，P<0.05）和中性粒细胞存在（r=0.72，P<0.01）呈正相关。在抗 TNF 加抗 P-选择素抗体组中，第 2 天和第 6 天的 IVC 壁中性粒细胞和总炎症细胞计数最低，第 13 天的中性粒细胞计数最低。该组的单核细胞流入在第 13 天也受到抑制。这些结果表明 TNF 和 P-选择素的联合中和在减轻静脉血栓形成引起的炎症中发挥着作用。
Venous thrombosis induces a detrimental inflammatory response in the vein wall. The cytokine tumor necrosis factor-α (TNF) and the adhesion molecules, selectins, have been found to be important in mediating inflammatory cell stimulation and leukocyte–endothelial cell adhesion, respectively. This study assesses the role of TNF and P-selectin in the inflammatory events associated with venous thrombosis. Rats were passively immunized with neutralizing anti-TNF serum alone, anti-TNF plus anti-P-selectin antibody, anti-P-selectin antibody alone, control serum, or control anti-P-selectin antibody. Antibodies or control sera were given prior to occlusion and at Days 2 and 4 postocclusion. Rats were sacrificed at Days 1–6 and Day 13 after occlusion for inferior vena caval (IVC) wall histopathology and TNF analysis. Differences in the extent of inflammatory cell infiltrate into the vein wall were found on Days 2, 6, and 13. TNF levels were elevated in the vein wall of the three groups not given anti-TNF antibody. The levels of TNF at Day 6 positively correlated with both total inflammatory cell (r= 0.53,P< 0.05) and neutrophil presence (r= 0.72,P< 0.01). The lowest IVC wall neutrophil and total inflammatory cell count at Days 2 and 6 and the lowest neutrophil count at Day 13 were found in the anti-TNF plus anti-P-selectin antibody group. Monocyte influx was also inhibited at Day 13 in this group. These results suggest a role for combined neutralization of TNF and P-selectin in the attenuation of inflammation induced by venous thrombosis.