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

Kirsten M. Pondman, MSc, Martin Sobik, MSc, Annapurna Nayak, MSc, Anthony G. Tsolaki, DPhil, Anne Jäkel, DPhil, Emmanuel Flahaut, PhD, Silke Hampel, PhD, Bennie ten Haken, PhD, Robert B. Sim, DPhil, Uday Kishore, PhD

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 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.

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