Toll样受体9活化在中性粒细胞损伤，并降低败血症中的结果*

蓝鱼o_0

Toll-like receptor 9 activation in neutrophils impairs chemotaxis and reduces sepsis outcome*
Silvia C. Trevelin, MSc; José C. Alves-Filho, PhD; Fabiane Sônego, MSc; Walter Turato, MSc;
Daniele C. Nascimento, PhD; Fabricio O. Souto, MSc; Thiago M. Cunha, PhD;
Ricardo T. Gazzinelli, PhD; Fernando Q. Cunha, PhD

Objectives: To investigate the role of toll-like receptor 9 on sepsis-induced failure of neutrophil recruitment to the site of infection.
Design: Prospective experimental study.
Setting: University research laboratory.
Interventions: Model of polymicrobial sepsis induced by cecal ligation and puncture in wild-type and toll-like receptor 9–deficient
mice.
Measurements and Main Results: Toll-like receptor 9–deficient mice with cecal ligation and puncture–induced severe sepsis did not demonstrate failure of neutrophil migration and consequently had a low systemic inflammatory response and a high survival rate. Upon investigating the mechanism by which toll-like receptor 9 deficiency prevents the failure of neutrophil migration, it was found that neutrophils derived from toll-like receptor 9–deficient
mice with cecal ligation and puncture–induced severe sepsis expressed high levels of chemokine C-X-C motif receptor 2 (CXCR2) and had reduced induction of G-protein–coupled receptor kinase 2.
Conclusions: These findings suggest that the poor outcome of severe sepsis is associated with toll-like receptor 9 activation in neutrophils, which triggers G-protein–coupled receptor kinase 2 expression and CXCR2 downregulation. These events account for the reduction of neutrophil migration to the site of infection, with consequent spreading of the infection, onset of the systemic inflammatory response, and a decrease in survival. (Crit Care Med 2012; 40:2631–2637)
Key Words: chemotaxis; CXCR2; failure of neutrophil migration; G-protein–coupled receptor kinase 2; sepsis; toll-like receptor 9

toll样受体在免疫中的作用越来越受到关注。本文从遗传学角度，进行了败血症病因学研究。


00003246-201209000-00013[1].pdf (1.22 MB, 下载次数: 0)

2012-9-12 17:05 上传

点击文件名下载附件

佳蕙淼淼

谢谢分享！感染学的新东东！