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Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

Findlay, Fern; Pohl, Jan; Svoboda, Pavel; Shakamuri, Priyanka; McLean, Kevin; Inglis, Neil F.; Proudfoot, Lorna; Barlow, Peter G.

Authors

Fern Findlay

Jan Pohl

Pavel Svoboda

Priyanka Shakamuri

Kevin McLean

Neil F. Inglis

Lorna Proudfoot



Abstract

Host defense peptides, also known as antimicrobial peptides, are key elements of innate host defense. One host defense peptide with well-characterized antimicrobial activity is the human cathelicidin, LL-37. LL-37 has been shown to be upregulated at sites of infection and inflammation and is regarded as one of the primary innate defense molecules against bacterial and viral infection. Human exposure to combustion-derived or engineered nanoparticles is of increasing concern, and the implications of nanomaterial exposure on the human immune response is poorly understood. However, it is widely acknowledged that nanoparticles can interact strongly with several immune proteins of biological significance, with these interactions resulting in structural and functional changes of the proteins involved. This study investigated whether the potent antibacterial and antiviral functions of LL-37 were inhibited by exposure to, and interaction with, carbon nanoparticles, together with characterizing the nature of the interaction. LL-37 was exposed to carbon black nanoparticles in vitro, and the antibacterial and antiviral functions of the peptide were subsequently assessed. We demonstrate a substantial loss of antimicrobial function when the peptide was exposed to low concentrations of nanomaterials, and we further show that the nanomaterial-peptide interaction resulted in a significant change in the structure of the peptide. The human health implications of these findings are significant, as, to our knowledge, this is the first evidence that nanoparticles can alter host defense peptide structure and function, indicating a new role for nanoparticle exposure in increased disease susceptibility.

Citation

Findlay, F., Pohl, J., Svoboda, P., Shakamuri, P., McLean, K., Inglis, N. F., Proudfoot, L., & Barlow, P. G. (2017). Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration. Journal of Immunology, 199(7), 2483-2490. https://doi.org/10.4049/jimmunol.1700706

Journal Article Type Article
Acceptance Date Jul 22, 2017
Online Publication Date Aug 16, 2017
Publication Date Oct 1, 2017
Deposit Date Jul 25, 2017
Journal Journal of Immunology
Print ISSN 0022-1767
Electronic ISSN 1550-6606
Publisher American Association of Immunologists
Peer Reviewed Peer Reviewed
Volume 199
Issue 7
Pages 2483-2490
DOI https://doi.org/10.4049/jimmunol.1700706
Keywords Carbon nanoparticles, antimicrobial activities, human cathelicidin LL-37,
Public URL http://researchrepository.napier.ac.uk/Output/966574