Isolation and characterization of pharmaceutical grade human pentraxins, serum amyloid P component and C-reactive protein, for clinical use

分离和表征用于临床的药物级人正五聚蛋白、血清淀粉样蛋白 P 成分和 C 反应蛋白

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作者:Mark B Pepys, J Ruth Gallimore, Joanne Lloyd, Zhanhong Li, David Graham, Graham W Taylor, Stephan Ellmerich, Palma P Mangione, Glenys A Tennent, Winston L Hutchinson, David J Millar, Gary Bennett, John More, David Evans, Yogesh Mistry, Stephen Poole, Philip N Hawkins

Abstract

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.

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