Increased C5a receptor expression in sepsis.
Increased C5a receptor expression in sepsis.
复制标题
脓毒症中 C5a 受体表达增加。
DOI：
10.1172/jci15409
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Ward,PeterA
中科院分区：
文献类型：
--
作者：
Riedemann,NielsC;Guo,Ren-Feng;Neff,ThomasA;Laudes,InesJ;Keller,KatieA;Sarma,VidyaJ;Markiewski,MaciejM;Mastellos,Dimitrios;Strey,ChristophW;Pierson,CarlL;Lambris,JohnD;Zetoune,FirasS;Ward,PeterA
在啮齿动物的脓毒症发展过程中，补体激活产物C5a的过度产生似乎是有害的。关于C5a受体(C5aR)在脓毒症中的作用及其在不同器官中的存在，人们知之甚少。在小鼠盲肠结扎/穿孔(CLP)模型上，我们发现在对照组和中性粒细胞耗竭的小鼠败血症早期，肺、肝、肾和心脏的C5aR免疫反应性显著增加。脓毒症时上述脏器中C5aR基因的表达也显著增加。免疫组织化学分析显示，CLP后，C5aR在所有四个器官的实质细胞中表达增加。与接受非特异性免疫球蛋白的小鼠相比，在CLP开始时注射C5aR阻断免疫球蛋白(αC5aR)的小鼠的存活率显著提高，注射αC5a的小鼠也是如此。与对照组相比，αC5aR处理组小鼠血清IL-6、α水平及各脏器细菌计数均显著降低。这些研究首次证明，在脓毒症的早期阶段，C5aR在肺、肝、肾和心脏中表达上调，阻断C5aR对脓毒症的致命后果具有高度的保护作用。
Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (αC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with αC5a. In αC5aR-treated mice, serum levels of IL-6 and TNF-α and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis.