Developmental Immunology Program, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Immunobiology. 2011 Jan-Feb;216(1-2):96-102. doi: 10.1016/j.imbio.2010.02.005. Epub 2010 Mar 4.
The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases.
宿主防御的第一道防线是先天免疫系统，其中包括凝血因子和模式识别分子，其中一种是甘露糖结合凝集素（MBL）。先前的研究表明，MBL 缺乏会增加感染的易感性。几种机制与增加感染的易感性有关，包括减少调理吞噬作用和减少凝集素补体途径的激活。在这项研究中，我们证明了 MBL 和 MBL 相关丝氨酸蛋白酶（MASP）-1/3 一起介导凝血因子样活性，包括类似凝血酶的活性。MBL 和/或 MASP-1/3 缺乏的宿主表现出体内证据，表明 MBL 和 MASP-1/3 参与损伤后的止血。金黄色葡萄球菌感染的 MBL 缺失小鼠发生弥散性血管内凝血（DIC），这与血液中白细胞介素 6 水平升高（但 TNF-α 和多器官炎症反应没有升高）有关。感染的 MBL 缺失小鼠也发生肝损伤。这些发现表明，MBL 缺乏可能在感染性疾病期间表现为 DIC 和器官衰竭。
