Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response

JOURNAL OF CONTROLLED RELEASE

卷:217

Article

Canova, Donata Federici¹  Pavlov, Anton M.^2,3  Norling, Lucy V.¹  Gobbetti, Thomas¹  Brunelleschi, Sandra⁴  Le Fauder, Pauline⁵  Cenac, Nicolas⁶  Sukhorukov, Gleb B.²  Perretti, Mauro¹ 

[1] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England

[2] Queen Mary Univ London, Sch Engn & Mat Sci, London EC1M 6BQ, England

[3] Saratov NG Chernyshevskii State Univ, Saratov, Russia

[4] Univ Piemonte Orientale, Dept Hlth Sci, Novara, Italy

[5] Fac Med Toulouse, INSERM, MetaToul Lipid Facil, UMR1046, F-31073 Toulouse, France

[6] Univ Toulouse 3, INSERM, UMR1043, Toulouse, France

关键词: Alpha-2-macroglobulin;    LbL microcapsules;    Inflammation;    Leukocyte activation;    Phagocytosis;   

DOI  :  10.1016/j.jconrel.2015.09.021

来源: Elsevier

【 摘 要 】

Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (alpha 2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with alpha 2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of alpha 2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble alpha 2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of alpha 2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of alpha 2MGZ with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis. (c) 2015 The Authors. Published by Elsevier B.V.

【 授权许可】

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