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

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 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. From the Clinical Editor: This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response.

Description
Keywords
C1q, Carbon nanotubes, Complement, Cytokines, Macrophage, Antigen-antibody reactions, Carbon nanotubes, Immune system, Macrophages, Anti-inflammatories, C1q, Cellular infiltration, Complement, Complement activations, Cytokines, Innate immune systems, Pro-inflammatory cytokines, Chemical activation, carbon nanotube, complement component C1q, complement component C3, complement component C5, complement membrane attack complex, interleukin 10, interleukin 12, interleukin 1beta, interleukin 6, messenger RNA, transforming growth factor beta, tumor necrosis factor alpha, carbon nanotube, complement component C1q, cytokine, animal cell, article, complement activation, complement deposition, cytokine response, down regulation, histiocyte, human, human cell, human tissue, macrophage, monocyte, nonhuman, opsonization, phagocytosis, U937 cell line, upregulation, cell line, complement activation, drug effects, immunology, macrophage, phagocytosis, ultrastructure, Cell Line, Complement Activation, Complement C1q, Cytokines, Humans, Macrophages, Nanotubes, Carbon, Phagocytosis
Citation
Pondman, K. M., Sobik, M., Nayak, A., Tsolaki, A. G., Jäkel, A., Flahaut, E., et al. (2014). Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages. 10(6). https://doi.org//10.1016/j.nano.2014.02.010
License
CC BY-NC-ND 3.0 Unported