Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, Rowland Hill Street, London NW3 2PF, UK.
J Immunol Methods. 2012 Oct 31;384(1-2):92-102. doi: 10.1016/j.jim.2012.07.013. Epub 2012 Jul 31.
The human pentraxin proteins, serum amyloid P component (SAP) and C-reactive protein (CRP) are important in routine clinical diagnosis, SAP for systemic amyloidosis and CRP for monitoring the non-specific acute phase response. They are also targets for novel therapies currently in development but their roles in health and disease are controversial. Thus, both for clinical use and to rigorously elucidate their functions, structurally and functionally intact, pharmaceutical grade preparations of the natural, authentic proteins are required. We report here the production from normal human donor plasma and the characterization of the first such preparations. Importantly, we demonstrate that, contrary to reports using recombinant proteins and less well characterized preparations, neither CRP nor SAP stimulate the release by human peripheral blood mononuclear cells in vitro of any TNFα, IL-6 or IL-8, nor does SAP cause release of IL-1β or IL-10. Furthermore neither of our preparations was pro-inflammatory in mice in vivo.
人 pentraxin 蛋白，血清淀粉样蛋白 P 成分（SAP）和 C 反应蛋白（CRP）在常规临床诊断中很重要，SAP 用于全身性淀粉样变性，CRP 用于监测非特异性急性期反应。它们也是目前正在开发的新型治疗方法的靶点，但它们在健康和疾病中的作用存在争议。因此，无论是用于临床应用还是为了严格阐明其功能，都需要具有结构和功能完整性的、药物级别的天然、真实蛋白质的制剂。我们在这里报告了从正常人类供体血浆中生产并对其进行了表征的第一批此类制剂。重要的是，我们证明，与使用重组蛋白和特征描述较差的制剂的报告相反，CRP 和 SAP 都不会刺激人外周血单核细胞在体外释放任何 TNFα、IL-6 或 IL-8，SAP 也不会导致 IL-1β 或 IL-10 的释放。此外，我们的制剂在体内都不会引起小鼠的炎症反应。
