Magnadóttir Bergljót, Hayes Polly, Gísladóttir Berglind, Bragason Birkir Þór, Hristova Mariya, Nicholas Anthony P, Guðmundsdóttir Sigríður, Lange Sigrun
Institute for Experimental Pathology, University of Iceland, Keldur v. Vesturlandsveg, 112 Reykjavik, Iceland.
Department of Biomedical Sciences, University of Westminster, London W1W 6UW, UK.
Dev Comp Immunol. 2018 Oct;87:1-11. doi: 10.1016/j.dci.2018.05.014. Epub 2018 May 17.
Pentraxins are fluid phase pattern recognition molecules that form an important part of the innate immune defence and are conserved between fish and human. In Atlantic cod (Gadus morhua L.), two pentraxin-like proteins have been described, CRP-I and CRP-II. Here we show for the first time that these two CRP forms are post-translationally deiminated (an irreversible conversion of arginine to citrulline) and differ with respect to tissue specific localisation in cod ontogeny from 3 to 84 days post hatching. While both forms are expressed in liver, albeit at temporally differing levels, CRP-I shows a strong association with nervous tissue while CRP-II is strongly associated to mucosal tissues of gut and skin. This indicates differing roles for the two pentraxin types in immune responses and tissue remodelling, also elucidating novel roles for CRP-I in the nervous system. The presence of deimination positive bands for cod CRPs varied somewhat between mucus and serum, possibly facilitating CRP protein moonlighting, allowing the same protein to exhibit a range of biological functions and thus meeting different functional requirements in different tissues. The presented findings may further current understanding of the diverse roles of pentraxins in teleost immune defences and tissue remodelling, as well as in various human pathologies, including autoimmune diseases, amyloidosis and cancer.
五聚素是液相模式识别分子,是固有免疫防御的重要组成部分,在鱼类和人类之间具有保守性。在大西洋鳕鱼(Gadus morhua L.)中,已描述了两种五聚素样蛋白,即CRP-I和CRP-II。在此,我们首次表明这两种CRP形式在翻译后发生脱亚氨基作用(精氨酸不可逆地转化为瓜氨酸),并且在孵化后3至84天的鳕鱼个体发育过程中,它们在组织特异性定位方面存在差异。虽然两种形式在肝脏中均有表达,尽管表达水平随时间有所不同,但CRP-I与神经组织有很强的关联,而CRP-II与肠道和皮肤的黏膜组织有很强的关联。这表明两种五聚素类型在免疫反应和组织重塑中具有不同的作用,也阐明了CRP-I在神经系统中的新作用。鳕鱼CRP的脱亚氨基阳性条带在黏液和血清中的存在情况有所不同,这可能有助于CRP的兼职功能,使同一蛋白质能够展现一系列生物学功能,从而满足不同组织中的不同功能需求。所呈现的研究结果可能会进一步加深我们对五聚素在硬骨鱼免疫防御和组织重塑以及包括自身免疫性疾病、淀粉样变性和癌症在内的各种人类病理学中的多种作用的理解。