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dc.contributor.authorØrning, Mathias Pontus
dc.contributor.authorHoem, Kine Samseth
dc.contributor.authorCoron, Abba Elizabeth
dc.contributor.authorSkjåk-Bræk, Gudmund
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorBrekke, Ole Lars
dc.contributor.authorEspevik, Terje
dc.contributor.authorRokstad, Anne Mari
dc.date.accessioned2016-10-03T14:15:47Z
dc.date.accessioned2016-10-10T09:32:39Z
dc.date.available2016-10-03T14:15:47Z
dc.date.available2016-10-10T09:32:39Z
dc.date.issued2016
dc.identifier.citationJournal of Controlled Release 2016, 229:58-69nb_NO
dc.identifier.issn1873-4995
dc.identifier.urihttp://hdl.handle.net/11250/2413839
dc.description.abstractThe inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-l-ornithine (PLO)-containing microcapsules, liquefied core poly-l-lysine (PLL)-containing microcapsules, and solid core PLL-containing microcapsules. No complement or inflammatory cytokine activation was detected for the Ca/Ba alginate microbeads. Liquefied core PLO- and PLL-containing microcapsules induced significant fluid phase complement activation (TCC), but with low complement surface deposition (anti-C3c), and a low proinflammatory cytokine secretion, with exception of an elevated MCP-1(CCL2) secretion. The solid core PLL-containing microcapsules generated lower TCC but a marked complement surface deposition and significant induction of the proinflammatory cytokines interleukin (IL-1)β, TNF, IL-6, the chemokines IL-8 (CXCL8), and MIP-1α (CCL3) and MCP-1(CCL2). Inhibition with compstatin (C3 inhibitor) completely abolished complement surface deposition, leukocyte adhesion and the proinflammatory cytokines. The C5 inhibitions partly lead to a reduction of the proinflammatory cytokines. The leukocyte adhesion was abolished by inhibitory antibodies against CD18 and partly reduced by CD11b, but not by CD11c. Anti-CD18 significantly reduced the (IL-1)β, TNF, IL-6 and MIP-1α and anti-CD11b significantly reduced the IL-6 and VEGF secretion. MCP-1 was strongly activated by anti-CD18 and anti-CD11b. In conclusion the initial proinflammatory cytokine responses are driven by the microspheres potential to trigger complement C3 (C3b/iC3b) deposition, leukocyte activation and binding through complement receptor CR3 (CD11b/CD18). MCP-1 is one exception dependent on the fluid phase complement activation mediated through CR3.nb_NO
dc.language.isoengnb_NO
dc.publisherElseviernb_NO
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0168365916301535
dc.titleAlginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activationnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.date.updated2016-10-03T14:15:47Z
dc.source.volume229nb_NO
dc.source.journalJournal of Controlled Releasenb_NO
dc.identifier.doi10.1016/j.jconrel.2016.03.021
dc.identifier.cristin1346665
dc.description.localcode© 2016 Elsevier B.V. All rights reserved. This is the authors' accepted and refereed manuscript to the article. Locked until 2017-05-10 due to the copyright restriction. Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License.nb_NO


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