中南大学Ben Lu课题组发现，肝素可预防caspase-11依赖的败血症致死，与其抗凝特性无关。该研究于2021年2月8日在线发表于国际一流学术期刊《免疫》。

研究人员表明，肝素可预防脓毒症中caspase-11依赖性免疫反应和致死性，而与其抗凝特性无关。肝素或无抗凝功能的化学修饰形式的肝素抑制了警报蛋白HMGB1-脂多糖（LPS）相互作用，并阻止了乙酰肝素酶巨噬细胞糖萼的降解。这些事件阻止了巨噬细胞中LPS的胞质传递和caspase-11的激活，后者是一种介导败血症致死性的胞质LPS受体。接受肝素治疗的败血症患者生存率高于未接受肝素治疗的患者。

对这种以前未知肝素功能的鉴定建立了先天免疫反应与凝血之间的联系。 

据了解，肝素是一种哺乳动物多糖，也是一种广泛用于治疗血栓形成疾病的抗凝药物。它还能够改善败血症的结局，败血症是由感染引起的免疫功能障碍导致死亡的主要原因。尽管相对清楚的是肝素如何发挥其抗凝作用，但肝素所能实现的免疫调节机制仍然是个谜。

附：英文原文

Title: Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties

Author: Yiting Tang, Xiangyu Wang, Zhaozheng Li, Zhihui He, Xinyu Yang, Xiaoye Cheng, Yue Peng, Qianqian Xue, Yang Bai, Rui Zhang, Kai Zhao, Fang Liang, Xianzhong Xiao, Ulf Andersson, Haichao Wang, Timothy R. Billiar, Ben Lu

Issue&Volume: 2021-02-08

Abstract: Heparin, a mammalian polysaccharide, is a widely used anticoagulant medicine to treatthrombotic disorders. It is also known to improve outcomes in sepsis, a leading causeof mortality resulted from infection-induced immune dysfunction. Whereas it is relativelyclear how heparin exerts its anticoagulant effect, the immunomodulatory mechanismsenabled by heparin remain enigmatic. Here, we show that heparin prevented caspase-11-dependentimmune responses and lethality in sepsis independent of its anticoagulant properties.Heparin or a chemically modified form of heparin without anticoagulant function inhibitedthe alarmin HMGB1-lipopolysaccharide (LPS) interaction and prevented the macrophageglycocalyx degradation by heparanase. These events blocked the cytosolic deliveryof LPS in macrophages and the activation of caspase-11, a cytosolic LPS receptor thatmediates lethality in sepsis. Survival was higher in septic patients treated withheparin than those without heparin treatment. The identification of this previouslyunrecognized heparin function establishes a link between innate immune responses andcoagulation.

DOI: 10.1016/j.immuni.2021.01.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00030-3