脂多糖结合蛋白和杀菌/通透性增加蛋白:脓毒症的潜在治疗靶点

Lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein: potential therapeutic targets in sepsis

脓毒症是严重感染、创伤、烧伤和休克等损伤的常见并发症和主要死因。革兰氏阴性菌细胞壁成分脂多糖(lipopolysaccharide, LPS)导致的内毒素血症是导致脓毒症的主要原因之一。包括脂多糖结合蛋白(lipopolysaccharide-binding protein, LBP)和杀菌/通透性增加蛋白(bactericidal permeability increasing protein, BPI)在内的多种血浆蛋白参与调控LPS激活的信号通路。两种蛋白属于同类蛋白家族,结构相似但生物学效应差异很大:LBP能协助LPS与靶细胞CD14受体结合增加宿主对LPS的敏感性,而BPI可中和LPS致炎作用并加速LPS从循环内清除。本文就LBP与BPI的结构、功能、治疗脓毒症的潜力及基因多态性与脓毒症的相关性等方面的研究进展进行综述。

Sepsis is a common complication of severe injuries, such as severe infection, trauma, burn, and shock, and it is the main cause of death of critically ill patients. Endotoxemia caused by lipopolysaccharides(LPS), cell wall components of gram-negative bacteria, is one of the main causes of sepsis. Multiple plasma proteins, including lipopolysaccharide binding proteins(LBP) and bactericidal permeability increase proteins(BPI), are involved in regulating the signaling pathways of LPS activation. The two proteins belong to the same family of proteins with similar structures but different biological functions: LBP facilitates LPS in binding to the CD14 receptor of target cells to increase host sensitivity to LPS, while BPI neutralizes the inflammatory effects of LPS and accelerates the clearance of LPS from the circulation. In this review, we summarized the research progress of LBP and BPI in terms of structure, function, potential for treatment of sepsis, and the correlation between gene polymorphisms and sepsis.