van Zoelen Marieke A D, Schmidt Ann-Marie, Florquin Sandrine, Meijers Joost C, de Beer Regina, de Vos Alex F, Nawroth Peter P, Bierhaus Angelika, van der Poll Tom
Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Infect Dis. 2009 Sep 1;200(5):765-73. doi: 10.1086/604730.
The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses.
To determine the role of RAGE in the innate immune response to abdominal sepsis caused by Escherichia coli, RAGE-deficient (RAGE(-/-)) and normal wild-type mice were intraperitoneally injected with E. coli. In a separate experiment, wild-type mice received either anti-RAGE immunoglobulin (Ig) G or control IgG.
E. coli sepsis resulted in an up-regulation of RAGE in the liver but not in the lungs. RAGE-deficient mice demonstrated an enhanced bacterial outgrowth in their peritoneal cavity and increased dissemination of the infection, accompanied by increased hepatocellular injury and exaggerated systemic cytokine release and coagulation activation, 20 h after intraperitoneal administration of E. coli. Wild-type mice treated with anti-RAGE IgG also displayed a diminished defense against the growth and/or dissemination of E. coli. RAGE was important for the initiation of the host response, as reflected by a reduced immune and procoagulant response early after intraperitoneal injection of E. coli lipopolysaccharide.
These data are the first to suggest that intact RAGE signaling contributes to an effective antibacterial defense during E. coli sepsis, thereby limiting the accompanying inflammatory and procoagulant response.
晚期糖基化终产物受体（RAGE）介导多种炎症反应。
为确定RAGE在对大肠杆菌引起的腹部脓毒症的固有免疫反应中的作用，将RAGE缺陷型（RAGE(-/-)）小鼠和正常野生型小鼠腹腔注射大肠杆菌。在另一项实验中，野生型小鼠接受抗RAGE免疫球蛋白（Ig）G或对照IgG。
大肠杆菌脓毒症导致肝脏中RAGE上调，但肺中未上调。腹腔注射大肠杆菌20小时后，RAGE缺陷型小鼠腹腔内细菌生长增强，感染播散增加，同时伴有肝细胞损伤加重、全身细胞因子释放和凝血激活加剧。用抗RAGE IgG处理的野生型小鼠对大肠杆菌的生长和/或播散的防御也减弱。RAGE对宿主反应的启动很重要，腹腔注射大肠杆菌脂多糖后早期免疫和促凝反应降低即反映了这一点。
这些数据首次表明，完整的RAGE信号传导有助于在大肠杆菌脓毒症期间进行有效的抗菌防御，从而限制伴随的炎症和促凝反应。
