Abstract:
C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca2+. The attention regarding the origin of CRP and its multifunctionality has gripped researchers for several decades. The reason can be traced to the integrated evolution of CRP in the animal kingdom. CRP has been unequivocally listed as a key indicator of infectious and inflammatory diseases including autoimmune diseases. The first occurrence of CRP in the evolutionary ladder appeared in arthropods followed by molluscs and much later in the chordates. The biological significance of CRP has been established in the animal kingdom starting from invertebrates. Interestingly, the site of synthesis of CRP is mainly the liver in vertebrates, while in invertebrates it is located in diverse tissues. CRP is a multifunctional player in the scenario of innate immunity. CRP acts as an opsonin in the area of complement activation and phagocytosis. Interestingly, CRP upregulates and downregulates both cytokine production and chemotaxis. Considering various studies of CRP in humans and non-human animals, it has been logically proposed that CRP plays a common role in animals. CRP also interacts with Fcγ receptors and triggers the inflammatory response of macrophages. CRP in other animals such as primates, fish, echinoderms, arthropods, and molluscs has also been studied in some detail which establishes the evolutionary significance of CRP. In mammals, the increase in CRP levels is an induced response to inflammation or trauma; interestingly, in arthropods and molluscs, CRP is constitutively expressed and represents a major component of their hemolymph. Investigations into the primary structure of CRP from various species revealed the overall relatedness between vertebrate and invertebrate CRP. Invertebrates lack an acquired immune response; they are therefore dependent on the multifunctional role of CRP leading to the evolutionary success of the invertebrate phyla.
摘要:
C反应蛋白(CRP)是急性期蛋白(APP)家族的主要成员之一。对这种CRP的兴趣是其对人类肺炎球菌感染的反应模式的开创性发现的结果。CRP具有与含磷酸胆碱物质反应的独特性质,如肺炎球菌C-多糖,在Ca2+的存在下。几十年来,人们对CRP的起源及其多功能性的关注一直困扰着研究人员。其原因可以追溯到动物界CRP的综合进化。CRP已被明确列为包括自身免疫性疾病在内的感染性和炎症性疾病的关键指标。在进化阶梯中,CRP的首次出现出现在节肢动物中,其次是软体动物,后来在脊索中出现。从无脊椎动物开始,已经在动物界建立了CRP的生物学意义。有趣的是,CRP的合成部位主要是脊椎动物的肝脏,而在无脊椎动物中,它位于不同的组织中。CRP是先天免疫场景中的多功能参与者。CRP在补体激活和吞噬作用方面充当调理素。有趣的是,CRP上调和下调细胞因子产生和趋化性。考虑到人类和非人类动物中CRP的各种研究,从逻辑上讲,CRP在动物中起着共同的作用。CRP还与Fcγ受体相互作用并触发巨噬细胞的炎症反应。其他动物如灵长类动物的CRP,鱼,棘皮动物,节肢动物,和软体动物也进行了一些详细的研究,建立了CRP的进化意义。在哺乳动物中,CRP水平的升高是对炎症或创伤的诱导反应;有趣的是,在节肢动物和软体动物中,CRP组成型表达并代表其血淋巴的主要成分。对来自不同物种的CRP的初级结构的研究揭示了脊椎动物和无脊椎动物CRP之间的整体相关性。无脊椎动物缺乏获得性免疫反应;因此,它们依赖于CRP的多功能作用,从而导致无脊椎动物门的进化成功。