Manley P N, Ancsin J B, Kisilevsky R
Department of Pathology and Molecular Medicine, Queen's University, Richardson Laboratory, Kingston, Ont., Canada K7L 3N6.
Med Hypotheses. 2006;66(4):784-92. doi: 10.1016/j.mehy.2005.10.018. Epub 2005 Dec 7.
Proteins that are highly conserved throughout evolution are presumed to have critical roles in the survival of the species. The two major acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA) increase up to 1000-fold during inflammation. Both proteins have been highly conserved phylogenetically for at least the last 500 million years. Thus far the physiologic role and the evolutionary significance of each remains uncertain and their potential interactions have been totally ignored despite a vast and accelerating scientific literature on the involvement of each in human disease. CRP is known to bind to phosphocholine in dead eukaryote and some live bacterial cell walls suggesting that CRP facilitates the phagocytosis of fragmented or intact dead cells and/or enhances host bacterial defenses. SAA has recently been shown to increase the rate of export of cholesterol of phagocytosed cell membranes from macrophages fourfold. We postulate that their combined physiological role is to facilitate the rapid endogenous recycling of cell membrane cholesterol and phospholipids during acute inflammation. CRP promotes efficient phagocytosis of dying cells by macrophages; SAA enhances the export of their free cholesterol/phospholipid for reuse in the membranes of the hundreds of billions of new cells required daily during acute inflammation and repair. The evolutionary conservation of these proteins in species from the horseshoe crab and echinoderms to humans suggests that the rapid endogenous recycling of cholesterol and phospholipids during the highly vulnerable period of acute inflammation is critical for their continual survival.
在整个进化过程中高度保守的蛋白质被认为在物种生存中发挥着关键作用。两种主要的急性期蛋白，即C反应蛋白（CRP）和血清淀粉样蛋白A（SAA），在炎症期间可增加高达1000倍。至少在过去的5亿年里，这两种蛋白在系统发育上一直高度保守。到目前为止，它们各自的生理作用和进化意义仍不明确，尽管关于它们各自在人类疾病中的参与有大量且不断加速增长的科学文献，但它们潜在的相互作用却完全被忽视了。已知CRP可与死亡真核生物和一些活细菌细胞壁中的磷酸胆碱结合，这表明CRP促进了破碎或完整死亡细胞的吞噬作用和/或增强了宿主对细菌的防御能力。最近研究表明，SAA可使巨噬细胞吞噬的细胞膜中胆固醇的输出速率提高四倍。我们推测它们共同的生理作用是在急性炎症期间促进细胞膜胆固醇和磷脂的快速内源性循环利用。CRP促进巨噬细胞对垂死细胞的有效吞噬作用；SAA增强其游离胆固醇/磷脂的输出，以便在急性炎症和修复期间每天所需的数千亿个新细胞的膜中重新利用。从鲎和棘皮动物到人类等物种中这些蛋白质的进化保守性表明，在急性炎症这个高度脆弱的时期，胆固醇和磷脂的快速内源性循环利用对它们的持续生存至关重要。
