Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages.

Pondman, Kirsten M, Sobik, Martin, Nayak, Annapurna, Tsolaki, Anthony G, Jäkel, Anne, Flahaut, Emmanuel, Hampel, Silke, Ten Haken, Bennie, Sim, Robert B. and Kishore, Uday (2014) Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages. Nanomedicine, 10(6), pp. 1287-1299. ISSN (print) 1549-9642

Official URL: http://dx.doi.org/10.1016/j.nano.2014.02.010

Abstract

Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used here continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. Carbon nanotubes (CNTs) are recognized by the innate immune system, especially by the classical pathway of the complement system. Complement activation is usually associated with a pro-inflammatory response. Here, we show that complement deposition on CMC- and RNA-CNTs can enhance their uptake by phagocytes, which in turn, leads to dampening of pro-inflammatory cytokine production. It appears that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by enhanced phagocytosis and suppression of cytokine storm.

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