dc.contributor.author | Ørning, Mathias Pontus | |
dc.contributor.author | Hoem, Kine Samseth | |
dc.contributor.author | Coron, Abba Elizabeth | |
dc.contributor.author | Skjåk-Bræk, Gudmund | |
dc.contributor.author | Mollnes, Tom Eirik | |
dc.contributor.author | Brekke, Ole Lars | |
dc.contributor.author | Espevik, Terje | |
dc.contributor.author | Rokstad, Anne Mari | |
dc.date.accessioned | 2016-10-03T14:15:47Z | |
dc.date.accessioned | 2016-10-10T09:32:39Z | |
dc.date.available | 2016-10-03T14:15:47Z | |
dc.date.available | 2016-10-10T09:32:39Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Journal of Controlled Release 2016, 229:58-69 | nb_NO |
dc.identifier.issn | 1873-4995 | |
dc.identifier.uri | http://hdl.handle.net/11250/2413839 | |
dc.description.abstract | The 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.iso | eng | nb_NO |
dc.publisher | Elsevier | nb_NO |
dc.relation.uri | http://www.sciencedirect.com/science/article/pii/S0168365916301535 | |
dc.title | Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.date.updated | 2016-10-03T14:15:47Z | |
dc.source.volume | 229 | nb_NO |
dc.source.journal | Journal of Controlled Release | nb_NO |
dc.identifier.doi | 10.1016/j.jconrel.2016.03.021 | |
dc.identifier.cristin | 1346665 | |
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 |