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.

先天免疫系统是一种敏感的非自我识别级联反应，由称为病原体相关分子模式 (PAMP) 的微生物细胞壁成分触发，例如革兰氏阴性细菌的脂多糖 (LPS)、真菌的 β-1,3-葡聚糖和革兰氏阳性细菌的肽聚糖通过一组称为模式识别受体的先天免疫系统种系编码受体进行识别。最近的研究表明，昆虫和甘露类通过细胞表面受体、Toll 和 Toll 样受体 (TLR) 保存先天免疫系统的信号传导途径。在哺乳动物中，专门抗原呈递细胞上的 TLR 通过以下方式发挥信号转导器的作用。 NF-kB，导致促炎细胞因子的产生和细胞表面刺激分子的表达，这是激活幼稚 T 细胞所必需的，TLR 可能作为信号传导在细胞膜上组装；在鲎先天免疫中，LPS诱导的颗粒血细胞胞吐作用是对抗传染性微生物的关键现象：LPS的刺激诱导储存在血细胞颗粒中的各种防御分子的分泌。 C 因子是一种识别 LPS 的丝氨酸蛋白酶酶原，可启动血淋巴凝固级联，也存在于血细胞表面。我们的数据表明，活化的 C 因子与 LPS 的复合物不是必需的，但蛋白水解活性是必需的，并且足以通过异三聚体 GTP 结合蛋白介导的信号通路触发胞吐作用。我们得出结论，丝氨酸蛋白酶原对血细胞功能起作用。作为 LPS 的模式识别受体。