Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover

Islam Hamad, A. Christy Hunter, Kenneth J. Rutt, Zhuang Liu, Hongjie Dai, S. Moein Moghimi

    Research output: Contribution to journalArticlepeer-review

    123 Scopus citations

    Abstract

    We have investigated the interaction between long circulating poly(ethylene glycol)-stabilized single-walled carbon nanotubes (SWNTs) and the complement system. Aminopoly(ethylene glycol)5000-distearoylphosphatidylethanolamine (aminoPEG5000-DSPE) and methoxyPEG5000-DSPE coated as-grown HIPco SWNTs activated complement in undiluted normal human serum as reflected in significant rises in C4d and SC5b-9 levels, but not the alternative pathway split-product Bb, thus indicating activation exclusively through C4 cleavage. Studies in C2-depleted serum confirmed that PEGylated nanotube-mediated elevation of SC5b-9 was C4b2a convertase-dependent. With the aid of monoclonal antibodies against C1s and human serum depleted from C1q, nanotube-mediated complement activation in C1q-depleted serum was also shown to be independent of classical pathway. Nanotube-mediated C4d elevation in C1q-depleted serum, however, was inhibited by N-acetylglucosamine, Futhan (a broad-spectrum serine protease inhibitor capable of preventing complement activation through all three pathways) and anti-MASP-2 antibodies; this strongly suggests a role for activation of MASP-2 in subsequent C4 cleavage and assembly of C4b2a covertases. Intravenous injection of PEGylated nanotubes in some rats was associated with a significant rise in plasma thromboxane B2 levels, indicative of in vivo nanotube-mediated complement activation. The clinical implications of these observations are discussed.

    Original languageEnglish (US)
    Pages (from-to)3797-3803
    Number of pages7
    JournalMolecular Immunology
    Volume45
    Issue number14
    DOIs
    StatePublished - Aug 2008

    Keywords

    • Biomaterials
    • C4
    • Carbon nanotubes
    • Complement system
    • Drug delivery system
    • Nanomedicine
    • SC5b-9

    ASJC Scopus subject areas

    • Molecular Biology
    • Immunology

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