A serine protease zymogen functions as a pattern-recognition receptor for lipopolysaccharides
A serine protease zymogen functions as a pattern-recognition receptor for lipopolysaccharides
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DOI：
10.1073/pnas.0306904101
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发表时间：
2004-01-27
影响因子：
11.1
通讯作者：
Kawabata, SI
中科院分区：
文献类型：
--
作者：
Ariki, S;Koori, K;Kawabata, SI
细菌脂多糖（LPS）诱导的颗粒血细胞的胞吐作用是鲎对感染性微生物的先天免疫的关键组成部分; LPS的刺激诱导颗粒血细胞分泌各种防御分子。使用先前未表征的胞吐试验，我们清楚地表明，血细胞只响应LPS，而不是其他病原体相关的分子模式，如β-1，3-葡聚糖和肽聚糖。此外，我们表明，一种颗粒状蛋白质称为因子C，LPS识别丝氨酸蛋白酶酶原，启动血淋巴凝血级联反应，也存在于血细胞表面作为LPS的生物传感器。我们的数据表明，C因子的蛋白水解活性是必要的，并足以触发胞吐通过异源三聚体GTP结合蛋白介导的信号通路。凝血酶不诱导血细胞的胞吐，但它是由对应于蛋白酶激活的G蛋白偶联受体（PARs）的拴系配体的六肽诱导的。这一发现表明血细胞表面存在PAR样受体。我们的结论是丝氨酸蛋白酶酶原的血细胞表面的功能作为模式识别蛋白的LPS。
Bacterial lipopolysaccharide (LPS)-induced exocytosis of granular hemocytes is a key component of the horseshoe crab's innate immunity to infectious microorganisms; stimulation by LPS induces the secretion of various defense molecules from the granular hemocytes. Using a previously uncharacterized assay for exocytosis, we clearly show that hemocytes respond only to LPS and not to other pathogen-associated molecular patterns, such as beta-1,3-glucans and peptidoglycans. Furthermore, we show that a granular protein called factor C, an LPS-recognizing serine protease zymogen that initiates the hemolymph coagulation cascade, also exists on the hemocyte surface as a biosensor for LPS. Our data demonstrate that the proteolytic activity of factor C is both necessary and sufficient to trigger exocytosis through a heterotrimeric GTP-binding protein-mediating signaling pathway. Exocytosis of hemocytes was not induced by thrombin, but it was induced by hexapeptides corresponding to the tethered ligands of protease-activated G protein-coupled receptors (PARs). This finding suggested the presence of a PAR-like receptor on the hemocyte surface. We conclude that the serine protease zymogen on the hemocyte surface functions as a pattern-recognition protein for LPS.