Keratinocyte-derived chemokine plays a critical role in the induction of systemic inflammation and tissue damage after trauma-hemorrhage
Keratinocyte-derived chemokine plays a critical role in the induction of systemic inflammation and tissue damage after trauma-hemorrhage
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DOI：
10.1097/shk.0b013e31814b8e0d
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发表时间：
2007-11-01
期刊：
影响因子：
3.1
通讯作者：
Chaudry, Irshad H.
中科院分区：
文献类型：
--
作者：
Frink, Michael;Hsieh, Ya-Ching;Chaudry, Irshad H.
中性粒细胞的渗入是创伤后器官功能障碍发生的关键步骤。我们先前已经证明，角质形成细胞衍生的趋化因子(KC)是一种中性粒细胞趋化因子，在创伤出血后上调。为了确定KC在创伤出血后的作用，我们检测了KC中和抗体对创伤后炎症反应的影响。手术前1小时，用抗KC抗体或同型对照处理雄性C3H/HEN小鼠。动物接受假手术或创伤-出血，然后用乳酸林格液复苏。2 h后处死，分离Kupffer细胞。采用双向流式细胞仪检测大鼠血浆中肿瘤坏死因子-α、白介素6、白介素10、单核细胞趋化蛋白1、巨噬细胞炎性蛋白1a和KC的水平、枯否细胞生成量和肺、肝组织中KC的含量。测定肺和肝脏髓过氧化物酶含量作为中性粒细胞浸润的指标，并测定这些器官的湿重/干重比。通过测定α-谷胱甘肽S转移酶浓度评价肝细胞损伤程度。创伤失血前应用抗KC抗体可阻止血浆中KC水平的升高，同时可减轻创伤失血后中性粒细胞的渗出和肺、肝组织的水肿形成。未观察到对血浆和库普弗细胞释放的其他细胞因子的影响。这些结果提示KC在创伤-出血和复苏后中性粒细胞浸润和器官损伤中起着关键作用。
Neutrophil infiltration is a crucial step in the development of organ dysfunction after trauma. We have previously shown that keratinocyte-derived chemokine (KC), a chemoattractant for neutrophils, is up-regulated after trauma-hemorrhage. To determine the role of KC after trauma-hemorrhage, the effect of a KC-neutralizing antibody on the posttraumatic inflammatory response was examined. One hour before surgery, male C3H/HeN mice were treated with an anti-KC antibody or isotype control. Animals were subjected to sham operation or trauma-hemorrhage and resuscitated with Ringer lactate thereafter. They were killed 2 h later, and Kupffer cells were isolated. Plasma levels, Kupffer cell production, and lung and liver content of TNF-alpha, IL-6, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1 a, and KC were determined by BID cytometric bead arrays. Myeloperoxidase content in lung and liver were measured as a parameter for neutrophil infiltration, and wet-to-dry weight ratios of these organs were also determined. Hepatocyte damage was assessed by measuring a-gluthathione S-transferase concentration. Administration of the anti-KC antibody before trauma-hemorrhage prevented increases in KC plasma levels, which was accompanied by amelioration of neutrophil infiltration and edema formation in lung and liver after trauma-hemorrhage. No effect on other cytokines in plasma or Kupffer cell release was observed. These results suggest that KC plays a pivotal role in neutrophil infiltration and organ damage after trauma-hemorrhage and resuscitation.