Activation of endothelial TLR2 by bacterial lipoprotein upregulates proteins specific for the neutrophil response.
Activation of endothelial TLR2 by bacterial lipoprotein upregulates proteins specific for the neutrophil response.
复制标题
细菌脂蛋白激活内皮 TLR2 上调中性粒细胞反应特异蛋白。
DOI：
10.1177/1753425911429336
复制
发表时间：
2012-08
期刊：
影响因子：
3.2
通讯作者：
Hellman J
中科院分区：
文献类型：
--
作者：
Wilhelmsen K;Mesa KR;Prakash A;Xu F;Hellman J
血管内皮在急性炎症性疾病如脓毒症期间整体参与宿主对感染的反应和器官衰竭。革兰氏阴性和革兰氏阳性细菌脂蛋白在脓毒症中循环，并且可以通过与内皮细胞（EC）Toll样受体2（TLR2）结合来直接激活内皮。在这份报告中，我们进行了最全面的分析，迄今为止的免疫相关基因的调节后，激活内皮细胞TLR2的细菌二酰化和三酰化脂肽。我们发现TLR2的激活特异性地诱导人脐静脉内皮细胞和人肺微血管内皮细胞表达IL 6、IL 8、CSF 2、CSF 3、ICAM 1和SELE。这些蛋白质参与炎症部位的中性粒细胞募集、粘附和活化。值得注意的是，我们的研究表明，TLR2介导的EC反应特别适合于中性粒细胞而不是单核白细胞的募集、活化和存活，EC不需要通过其他炎症刺激来启动以响应细菌脂肽，并且与单核白细胞不同，TLR2激动剂不诱导EC分泌TNFα。这项研究表明，内皮细胞TLR2可能是一个重要的调节中性粒细胞运输到感染部位的一般，肺内皮细胞TLR2的直接激活可能有助于急性肺损伤脓毒症。
The vascular endothelium is integrally involved in the host response to infection and in organ failure during acute inflammatory disorders such as sepsis. Gram-negative and gram-positive bacterial lipoproteins circulate in sepsis and can directly activate the endothelium by binding to endothelial cell (EC) Toll-like receptor 2 (TLR2). In this report, we perform the most comprehensive analysis to date of the immune-related genes regulated after activation of endothelial TLR2 by bacterial di- and triacylated lipopeptides. We found that TLR2 activation specifically induces the expression of IL6, IL8, CSF2, CSF3, ICAM1 and SELE by human umbilical vein ECs and human lung microvascular ECs. These proteins participate in neutrophil recruitment, adherence and activation at sites of inflammation. Significantly, our studies demonstrate that TLR2-mediated EC responses are specifically geared towards recruitment, activation, and survival of neutrophils and not mononuclear leukocytes, that ECs do not require priming by other inflammatory stimuli to respond to bacterial lipopeptides and unlike mononuclear leukocytes, TLR2 agonists do not induce ECs to secrete TNFα. This study suggests that endothelial TLR2 may be an important regulator of neutrophil trafficking to sites of infection in general, and that direct activation of lung endothelial TLR2 may contribute to acute lung injury during sepsis.
登录
查看更多内容
影响因子：
15.9
作者：
Andonegui, G;Bonder, CS;Kubes, P
通讯作者：
Kubes, P
影响因子：
4.4
作者：
Faure, E;Thomas, L;Arditi, M
通讯作者：
Arditi, M
影响因子：
5.4
作者：
Gillrie, Mark R.;Zbytnuik, Lori;Ho, May
通讯作者：
Ho, May
DOI：
10.1016/0192-0561(95)00025-w
发表时间：
1995-05-01
期刊：
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子：
--
作者：
BOBER, LA;GRACE, MJ;NARULA, SK
通讯作者：
NARULA, SK
影响因子：
14.9
作者：
Edgar, R;Domrachev, M;Lash, AE
通讯作者：
Lash, AE