A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting.
A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting.
复制标题
DOI：
10.1016/j.ijpara.2014.01.010
复制
发表时间：
2014-05
影响因子：
4
通讯作者：
Mulenga A
中科院分区：
文献类型：
--
作者：
Ibelli AM;Kim TK;Hill CC;Lewis LA;Bakshi M;Miller S;Porter L;Mulenga A
肩突硬蜱是一种医学上重要的蜱种，可传播重要的人类蜱传疾病（包括疏螺旋体病、无形体病和巴贝斯虫病）的病原体。在开发新方法以保护人类免受蜱传疾病感染之前，需要了解这种蜱虫是如何进食的。这项研究的特点是血餐诱导的I。肩胛蜱（Ixsc）蜱唾液丝氨酸蛋白酶抑制剂（serpin（S）），内部称为IxscS-1E1。蜱使用丝氨酸蛋白酶抑制剂逃避宿主对蜱摄食的防御反应的假设是基于蜱丝氨酸蛋白酶抑制剂抑制宿主抗蜱防御反应的蛋白酶介体的功能的假设。因此，重要的是，与抑制性丝氨酸蛋白酶抑制剂的标志性特征一致，巴斯德毕赤酵母表达的重组IxscS-1E1（rIxscS-1E1）可以将凝血酶和胰蛋白酶捕获在SDS和热稳定复合物中，并且以剂量响应的方式降低这两种蛋白酶的活性。此外，rIxscS-1E1也抑制组织蛋白酶G和因子Xa，但显然不与它们形成可检测的复合物。我们的数据还表明，即使在高得多的rIxscS-1E1浓度下，rIxscS-1E1也可能不抑制糜蛋白酶、激肽释放酶、糜蛋白酶、纤溶酶、弹性蛋白酶和木瓜蛋白酶。天然IxscS-1E1可能在促进I. rIxscS-1E1抑制二磷酸腺苷（ADP）和凝血酶激活的血小板聚集，并以剂量响应方式延迟激活的部分凝血酶原时间（APTT）和凝血酶时间（TT）血浆凝血的能力揭示了肩胛蜱逃避宿主的止血防御。我们的结论是，本地IxscS-1E1是蜱唾液蛋白复合物的一部分，介导其抗止血，并潜在的炎症，通过抑制凝血酶，胰蛋白酶和其他未知的胰蛋白酶样蛋白酶在蜱宿主界面的作用功能。
Ixodes scapularis is a medically important tick species that transmits causative agents of important human tick-borne diseases including borreliosis, anaplasmosis and babesiosis. An understanding of how this tick feeds is needed prior to the development of novel methods to protect the human population against tick-borne disease infections. This study characterizes a blood meal-induced I. scapularis (Ixsc) tick saliva serine protease inhibitor (serpin (S)), in-house referred to as IxscS-1E1. The hypothesis that ticks use serpins to evade the host's defense response to tick feeding is based on the assumption that tick serpins inhibit functions of protease mediators of the host's anti-tick defense response. Thus, it is significant that consistent with hallmark characteristics of inhibitory serpins, Pichia pastoris-expressed recombinant IxscS-1E1 (rIxscS-1E1) can trap thrombin and trypsin in SDS- and heat-stable complexes, and reduce the activity of the two proteases in a dose-responsive manner. Additionally, rIxscS-1E1 also inhibited, but did not apparently form detectable complexes with, cathepsin G and factor Xa. Our data also show that rIxscS-1E1 may not inhibit chymotrypsin, kallikrein, chymase, plasmin, elastase and papain even at a much higher rIxscS-1E1 concentration. Native IxscS-1E1 potentially plays a role(s) in facilitating I. scapularis tick evasion of the host's hemostatic defense as revealed by the ability of rIxscS-1E1 to inhibit adenosine diphosphate (ADP)- and thrombin-activated platelet aggregation, and delay activated partial prothrombin time (APTT) and thrombin time (TT) plasma clotting in a dose-responsive manner. We conclude that native IxscS-1E1 is part of the tick saliva protein complex that mediates its anti-hemostatic, and potentially inflammatory, functions by inhibiting the actions of thrombin, trypsin and other yet unknown trypsin-like proteases at the tick-host interface.
登录
查看更多内容
DOI：
10.4269/ajtmh.2004.71.3.0700268
发表时间：
2004-09-01
影响因子：
3.3
作者：
Ebel, GD;Kramer, LD
通讯作者：
Kramer, LD
影响因子：
2.2
作者：
Guaratini Ibelli, Adriana Mercia;Hermance, Meghan M.;Kim, Tae Kwon;Gonzalez, Cassandra Lee;Mulenga, Albert
通讯作者：
Mulenga, Albert
影响因子：
3.7
作者：
Karim S;Singh P;Ribeiro JM
通讯作者：
Ribeiro JM
影响因子：
5.5
作者：
Imamura, S;Namangala, B;Onuma, M
通讯作者：
Onuma, M
DOI：
10.4269/ajtmh.2002.66.225
发表时间：
2002-03-01
影响因子：
3.3
作者：
Leboulle, G;Rochez, C;Godfroid, E
通讯作者：
Godfroid, E