Structural Analysis of Lipopolysaccharide-receptor on hemocytes of horseshoe crab

鲎血细胞脂多糖受体的结构分析

基本信息

批准号：
13680693
负责人：
KAWABATA Shun-ichiro
金额：
$ 2.69万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680693/
关键词：
Gram-negative bacteria Exocytosis Lipopolysaccharide LPS receptor G protein カブトガニ LPS リピドA

项目摘要

The innate immune system is a sensitive non-self-recognizing cascade triggered by microbial cell wall constituents called pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides (LPS) of Gram-negative bacteria, β-1,3-glucans of fungi, and peptidoglycans of Gram-positive bacteria. These PAMPs are recognized via a set of germ line-encoded receptros of innate immune system called pattern recognition receptors. Recent studies have revealed that insects and mannals conserve a signaling pathway of the innate immune system through cell-surface receptors, Toll and Toll-like receptors (TLRs). In mammals, TLRs on specialized antigen-presenting cells function as signal transducers by way of NF-kB, leading to the production of pro-inflammatory cytokines and the expression of constimulatory molecules on the cell surface, which are necessary to activate naive T cells; TLRs are possibly assembled at the cell membrane as signaling receptor complexes. In the horseshoe crab innate immunity, LPS-induced exocytosis of granular hemocytes is a key phenomenon to fight infectious microorganisms: the stimulation by LPS induces the secretion of various defense molecules stored in granules of hemocytes. Here we show that a granular component factor C, an LPS-recognizing serine protease zymogen initiating the hemolymph coagulation cascade, also exists on the surface of hemocytes. Our data demonstrate that the complex of the activated factor C with LPS is not required but the proteolytic activity is required and sufficient to trigger the exocytosis through a heterotrimeric GTP-binding protein-mediating signaling pathway. We conclude that the serine protease zymogen on hemocytes functions as a pattern recognition receptor for LPS.

先天性免疫系统是由微生物细胞壁触发的敏感的非自我认识的级联反应，该级联壁构成了病原体相关的分子模式（PAMP），例如革兰氏阴性细菌的脂多糖（LPS），β-1,3-葡萄糖的fungi和cungi和pepper-posisteria。这些弹药通过一组称为模式识别受体的固有免疫系统的种系编码受体识别。最近的研究表明，绝缘层和甘露纳斯通过细胞表面受体，收费和收费受体（TLR）保存先天免疫系统的信号传导途径。在哺乳动物中，专门的抗原呈递细胞上的TLR通过NF-KB充当信号传感器，导致产生促炎性细胞因子的产生，以及在细胞表面上的残留分子的表达，这对于激活幼稚T细胞是必不可少的；可能会在细胞膜上组装TLR作为信号接收器配合物。在马蹄螃蟹先天免疫中，LPS诱导的颗粒状血细胞胞胞病是抵抗传染性微生物的关键现象：LPS刺激诱导在血细胞颗粒中存储的各种防御分子的分泌。在这里，我们表明，颗粒状成分因子C（一种lps识别的丝氨酸蛋白酶原启动了血淋巴凝血级联反应）也存在于血细胞表面上。我们的数据表明，激活因子C与LP的复合物不需要，但是需要蛋白水解活性，足以通过异三体二聚体结合蛋白质介导的信号传导途径触发胞吐作用。我们包括血细胞上的丝氨酸蛋白酶原充当LPS的模式识别受体。