Factor C Acts as a Lipopolysaccharide-Responsive C3 Convertase in Horseshoe Crab Complement Activation
Factor C Acts as a Lipopolysaccharide-Responsive C3 Convertase in Horseshoe Crab Complement Activation
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DOI：
10.4049/jimmunol.181.11.7994
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发表时间：
2008-12-01
影响因子：
4.4
通讯作者：
Kawabata, Shun-ichiro
中科院分区：
文献类型：
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作者：
Ariki, Shigeru;Takahara, Shusaku;Kawabata, Shun-ichiro
脊椎动物中的补体系统在宿主防御和清除入侵微生物中起着重要作用，其中补体成分C3在病原体的调理中起着重要作用，而无脊椎动物补体C3激活的分子机制尚不清楚。为了了解无脊椎动物C3的分子激活机制，我们从河蟹Tachypleus tridentatus中分离并鉴定了C3的一个同源基因(命名为TtC3)。用抗TtC3抗体进行的流式细胞术分析表明，马蹄蟹补体系统对革兰氏阴性和革兰氏阳性细菌都有调理作用。对各种病原体相关分子模式在血蓝蛋白耗竭血浆中促进TtC3到TtC3b的蛋白水解性转换的能力的评估表明，强烈诱导这种转换的是嘴唇，而不是酵母多糖、肽聚糖或海带多糖，这突显了补体系统对嘴唇刺激的选择性反应。虽然最初的特征是储存在血细胞内的内毒素敏感的启动物或血淋巴凝结，但我们在血淋巴血浆中发现了C因子。抗C因子抗体可抑制内毒素诱导的多种现象，包括血浆酰胺酶活性、TtC3的蛋白分解活性以及TtC3b在革兰氏阴性菌表面的沉积。此外，革兰氏阴性菌表面存在的活化因子C直接催化纯化的TtC3的蛋白水解性转化，从而促进TtC3b的沉积。我们的结论是，在马蹄蟹补体激活的初始阶段，因子C在入侵的革兰氏阴性菌表面起到了内毒素反应C3转换酶的作用。免疫学杂志，2008,181：7994-8001。
The complement system in vertebrates plays an important role in host defense against and clearance of invading microbes, in which complement component C3 plays an essential role in the opsonization of pathogens, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. In an effort to understand the molecular activation mechanism of invertebrate C3, we isolated and characterized an ortholog of C3 (designated TtC3) from the horseshoe crab Tachypleus tridentatus. Flow cytometric analysis using an Ab against TtC3 revealed that the horseshoe crab complement system opsonizes both Gram-negative and Gram-positive bacteria. Evaluation of the ability of various pathogen-associated molecular patterns to promote the proteolytic conversion of TtC3 to TtC3b in hemocyanin-depleted plasma indicated that LIPS, but not zymosan, peptidoglycan, or laminarin, strongly induces this conversion, highlighting the selective response of the complement system to LIPS stimulation. Although originally characterized as an LPS-sensitive initiator or hemolymph coagulation stored within hemocytes, we identified factor C in hemolymph plasma. An anti-factor C Ab inhibited various LPS-induced phenomena, including plasma amidase activity, the proteolytic activation of TtC3, and the deposition of TtC3b on the surface of Gram-negative bacteria. Moreover, activated factor C present on the surface of Gram-negative bacteria directly catalyzed the proteolytic conversion of the purified TtC3, thereby promoting TtC3b deposition. We conclude that factor C acts as an LPS-responsive C3 convertase on the surface of invading Gram-negative bacteria in the initial phase of horseshoe crab complement activation. The Journal of Immunology, 2008, 181: 7994-8001.