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. 2008 Oct;87(1):129-35.
doi: 10.1002/jbm.a.31750.

The Artificial Surface-Induced Whole Blood Inflammatory Reaction Revealed by Increases in a Series of Chemokines and Growth Factors Is Largely Complement Dependent

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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

K T Lappegård et al. J Biomed Mater Res A. .
Free PMC article

Abstract

Exposing blood to an artificial surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the artificial surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1alpha, MIP-1beta, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1beta, TNFalpha and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC surface was used as negative control and completely abolished the whole inflammatory response. The artificial surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.

Figures

Figure 1
Figure 1
Median concentration in arbitrary units/mL (with 25–75 percentiles) for the terminal complement complex (TCC). T0, baseline values; PVC, polyvinyl chloride loops; Comp, PVC loops with compstatin; Hep, heparin-coated loops; Control, control peptide. Loops incubated at 37°C for 4 h. p < 0.05 for PVC versus T0, and p < 0.05 for compstatin versus PVC.
Figure 2
Figure 2
Median concentration in pg/mL (with 25–75 percentiles) for interleukin 8 (IL-8, left panel) and monocyte chemoattractant protein 1 (MCP-1, right panel). Loops incubated at 37°C for 4 h. p < 0.05 for PVC versus T0, and p < 0.05 for compstatin versus PVC. N = 8–10.
Figure 3
Figure 3
Median concentration in pg/mL (with 25–75 percentiles) for macrophage inflammatory protein-1-alpha (MIP-1α, left panel) and macrophage inflammatory protein-1-beta (MIP-1β, right panel). Loops incubated at 37°C for 4 h. p < 0.05 for PVC versus T0, and p < 0.05 for compstatin versus PVC. N = 8–10.
Figure 4
Figure 4
Median concentration in pg/mL (with 25–75 percentiles) for regulated upon activation T cell expressed and secreted (RANTES, left panel) and eotaxin (right panel). Loops incubated at 37°C for 4 h. p < 0.05 for PVC versus T0, and p < 0.05 for compstatin versus PVC. N = 8–10.
Figure 5
Figure 5
Median concentration in pg/mL (with 25–75 percentiles) for granulocyte colony stimulating factor (G-CSF, left panel) and granulocyte-macrophage colony stimulating factor (GM-CSF, right panel). Loops incubated at 37°C for 4 h. p < 0.05 for PVC versus T0, and p < 0.05 for compstatin versus PVC. N = 8–10.
Figure 6
Figure 6
Median concentration in pg/mL (with 25–75 percentiles) for vascular endothelial growth factor (VEGF, left panel) and platelet-derived growth factor-BB (PDGF, right panel). Loops incubated at 37°C for 4 h. p < 0.05 for PVC versus T0, and p < 0.05 for compstatin versus PVC. N = 8–10.
Figure 7
Figure 7
Median concentration in pg/mL (with 25–75 percentiles) for interleukin 6 (IL-6). LAM, laminaran-coated loops. N = 4, unsufficient for statistical calculations. Loops incubated at 37°C for 4 h.

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