Severe multiple organ injury in HSF1 knockout mice induced by lipopolysaccharide is associated with an increase in neutrophil infiltration and surface expression of adhesion molecules
Severe multiple organ injury in HSF1 knockout mice induced by lipopolysaccharide is associated with an increase in neutrophil infiltration and surface expression of adhesion molecules
复制标题
脂多糖诱导的HSF1敲除小鼠的严重多器官损伤与中性粒细胞浸润和粘附分子表面表达的增加有关
DOI：
10.1189/jlb.0212060
复制
发表时间：
2012-10-01
影响因子：
5.5
通讯作者：
Xiao, Xianzhong
中科院分区：
文献类型：
--
作者：
Chen, Shuhua;Zuo, Xiaoxia;Xiao, Xianzhong
我们以前曾报道过，HSF 1是必不可少的保护对致命的全身炎症诱导的LPS。然而，HSF 1保护免受LPS诱导的全身性炎症的机制仍然未知。在本研究中，通过快速注射LPS（10 mg/kg，i. p.）使HSF 1（-/-）小鼠经受内毒素血症。检测血清LDH、BUN、ALT、AST水平。免疫组化法观察内毒素血症后肺、肝、肾组织中PMN浸润情况。与WT对照组相比，LPS给药导致HSF 1（-/-）小鼠更严重的多器官功能障碍和更低的存活率。此外，HSF 1（-/-）小鼠肺、肝和肾中的PMN浸润多于WT小鼠。HSF 1（-/-）小鼠组织中PMN浸润增加与其在体内增强的内皮粘附特性有关。另外，LPS处理后，HSF 1（-/-）可诱导PMN表面PSGL-1和CD 11b表达增加。这些结果表明，HSF 1通过抑制PMNs表面粘附分子的表达和随后的PMNs在组织中的浸润来减轻LPS诱导的小鼠多器官损伤。J. Leukoc. 92：851-857; 2012.
We have reported previously that HSF1 is essential in protection against the lethal systemic inflammation induced by LPS. However, the mechanism by which HSF1 protects against LPS-induced systemic inflammation remains unknown. In this study, HSF1(-/-) mice were subjected to endotoxemia by a bolus injection of LPS (10 mg/kg, i.p.). The serum levels of LDH, BUN, and transaminase (ALT and AST) were measured. PMN infiltration in lung, liver, and kidney tissues after endotoxemia was observed with immunohistochemistry. Comparing with the WT control, LPS administration induced more severe multiple organ dysfunction and lower survival rates in the HSF1(-/-) mice. Moreover, PMN infiltration into lungs, liver, and kidneys in HSF1(-/-) mice was more than that in the WT mice. The augmented tissue PMN infiltration in HSF1(-/-) mice was associated with their enhanced adhesive properties to endothelium in vivo. In addition, HSF1(-/-) caused greater surface expression of PSGL-1 and CD11b on the PMN surface after LPS treatment. These findings suggested that HSF1 alleviated LPS-induced multiple organ injury in mice by suppressing the surface expression of adhesion molecules on PMNs and subsequent infiltration of PMNs in tissues. J. Leukoc. Biol. 92: 851-857; 2012.