The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent

Lappegård, Knut Tore; Bergseth, Grethe; Riesenfeld, Johan; Pharo, Anne; Magotti, Paola; Lambris, John D.; Mollnes, Tom Eirik

doi:10.1002/jbm.a.31750

Cited by 43 publications

(32 citation statements)

References 19 publications

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“…Our results demonstrated that both C3a and C5a are major contributors to the release of pro-inflammatory cytokines, since both inhibition of C3 and C5 as well as C3aR and 25 Furthermore, a complete dependency on complement has previously also been found for the inflammatory cytokines IL-1β, TNF, IL-6, IL-8, MIP-1β and MCP-1 during exposure to poly-l-lysine containing microcapsules. 18 To the best of our knowledge, this is the first study that showed that engineered nanoparticles, like IONPs, induce cytokine secretion in a complementdependent manner, thus underscoring the potential of inhibiting complement to prevent detrimental coagulation-and inflammation-related effects induced by nanoparticles.…”

Section: Discussionsupporting

confidence: 72%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood.

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Section: Discussionsupporting

confidence: 72%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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“…The activation of the complement system is one of the most significant challenges when blood is exposed to foreign materials 16, 17, 18, 19. Measures of C3a and SC5b‐9, also called Terminal Complement Complex (TCC), are widely used as complement activation markers.…”

Section: Methodsmentioning

confidence: 99%

Improved ex vivo blood compatibility of central venous catheter with noble metal alloy coating

et al. 2015

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Central line associated bloodstream infections (CLABSIs) are a serious cause of morbidity and mortality induced by the use of central venous catheters (CVCs). Nobel metal alloy (NMA) coating is an advanced surface modification that prevents microbial adhesion and growth on catheters and thereby reduces the risk of infection. In vitro microbiological analyses have shown up to 90% reduction in microbial adhesion on coated CVC compared to uncoated ones. This study aimed to assess the blood compatibility of NMA‐coated CVC according to ISO 10993‐4. Hemolysis, thrombin–antithrombin (TAT) complex, platelet counts, fibrin deposition, and C3a and SC5b‐9 complement activation were analyzed in human blood exposed to the NMA‐coated and control CVCs using a Chandler‐loop model. NMA‐coated CVC did not induce hemolysis and fell in the “nonhemolytic” category according to ASTM F756‐00. Significantly lower amounts of TAT were generated and less fibrin was deposited on NMA‐coated CVC than on uncoated ones. Slightly higher platelet counts and lower complement markers were observed for NMA‐coated CVC compared to uncoated ones. These data suggest that the NMA‐coated CVC has better ex vivo blood compatibility compared to uncoated CVC. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1359–1365, 2016.

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“…In addition, C3 is found in the peritoneal fluid [8] as well as in subcutaneous and omental adipose tissue [9]. C3 is a contributor to the biomaterial-induced inflammation during blood contact [10], and recently C3 was demonstrated to be involved in the inflammatory host response against subcutaneous and intraperitoneally implanted…”

Section: Introductionmentioning

confidence: 99%

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

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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 PLLcontaining 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.

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The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent

Cited by 43 publications

References 19 publications

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Improved ex vivo blood compatibility of central venous catheter with noble metal alloy coating

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

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