Ficolins:: Novel pattern recognition molecules of the innate immune response
Ficolins:: Novel pattern recognition molecules of the innate immune response
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DOI：
10.1016/j.imbio.2007.10.009
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发表时间：
2008-01-01
期刊：
影响因子：
2.8
通讯作者：
Maennel, Damela N.
中科院分区：
文献类型：
--
作者：
Runza, Valeria L.;Schwaeble, Wilhelm;Maennel, Damela N.
无花果蛋白酶是能够识别微生物表面上的病原体相关分子模式（PAMP）的蛋白质的聚集蛋白家族的成员。在与其特异性PAMP结合后，纤维胶凝蛋白可以通过与胶原凝集素的细胞受体结合或通过经由凝集素途径启动补体的活化来触发免疫系统的活化。对于后者，人纤维胶凝蛋白（即L-、H-和M-纤维胶凝蛋白）和鼠纤维胶凝蛋白-A显示与凝集素途径特异性丝氨酸蛋白酶MBL相关的丝氨酸蛋白酶-2（MASP-2）缔合并催化其活化，其继而活化C4和C4 b结合的C2以产生C3转化酶C4 b2 a。越来越多的证据强调纤维胶凝蛋白的凝集素性质，其具有在微生物表面上识别的广泛的碳水化合物部分。然而，并非纤维胶凝蛋白家族的所有成员似乎都充当凝集素途径识别组分。例如，鼠纤维胶凝蛋白-B不与MASP-2缔合，并且似乎不存在于血浆和其它体液中。其严格的细胞定位指向免疫应答中的其他功能，可能充当细胞内清除剂以靶向并促进携带PAMP的碎片的清除。当比较来自不同物种的纤维胶凝蛋白直向同源物时，很明显，人、鼠和猪的纤维胶凝蛋白在许多方面不同，这是我们在本次审查中旨在解决的一个具体问题。(C)2007年，Elsevier GmbH。All rights reserved.
Ficolins are members of the collectin family of proteins which are able to recognize pathogen-associated molecular pattern (PAMP) on microbial surfaces. Upon binding to their specific PAMP, ficolins may trigger activation of the immune system by either binding to cellular receptors for collectins or by initiating activation of complement via the lectin pathway. For the latter, the human ficolins (i.e. L-, H- and M-ficolin) and murine ficolin-A were shown to associate with the lectin pathway-specific serine protease MBL-associated serine protease-2 (MASP-2) and catalyse its activation which in turn activates C4 and C4b-bound C2 to generate the C3 convertase C4b2a. There is mounting evidence underlining the lectin nature of ficolins with a wide range of carbohydrate moieties recognized on microbial surfaces. However, not all members of the ficolin family appear to act as lectin pathway recognition components. For example, murine ficolin-B does not associate with MASP-2 and appears to be absent in plasma and other humoral fluids. Its stringent cellular localization points to other functions within the immune response, possibly acting as an intracellular scavenger to target and facilitate clearance of PAMP-bearing debris. When comparing ficolin orthologues from different species, it appears evident that human, murine, and porcine ficolins differ in many aspects, a specific point that we aim to address in this review. (C) 2007 Elsevier GmbH. All rights reserved.