Open Access

ARTICLE

Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles

Marilena Lucarelli¹, Antonietta M. Gatti², Graziana Savarino¹, Paola Quattroni¹, Lucia Martinelli¹, Emanuela Monari², Diana Boraschi¹

1 Unit of Immunobiology, Institute of Biomedical Technologies, CNR, Via Moruzzi 1, I-56124 Pisa, Italy
2 Laboratory of Biomaterials, University of Modena, National Institute of Material Physics (INFM), Via del Pozzo 71, I-41100 Modena, Italy

* Corresponding Author: D. Boraschi,

European Cytokine Network 2004, 15(4), 339-346.

Accepted 05 October 2004;

Abstract

Nano-sized particles of ceramic and metallic materials are generated by high-tech industrial activities, and can be generated from worn-out replacement and prosthetic implants. The interaction with the human body of such nanoparticles has been investigated, with a particular emphasis on innate defence mechanisms. Human macrophages (PMA-differentiated myelomonocytic U-937 cells) were exposed in vitro to non-toxic concentrations of TiO₂, SiO₂, ZrO₂, or Co nanoparticles, and their inflammatory response (expression of TLR receptors and co-receptors, and cytokine production) was examined. Expression of TLR receptors was generally unaffected by exposure to the different nanoparticles, except for some notable cases. Exposure to nanoparticles of ZrO₂ (and to a lesser extent TiO₂), upregulated expression of viral TLR receptors TLR3 and TLR7. Expression of TLR10 was also increased by TiO₂ and ZrO₂ nanoparticles. On the other hand, TLR9 expression was decreased by SiO₂ nano-particles, and expression of the co-receptor CD14 was inhibited by Co nanoparticles. Basal and LPS-induced production of cytokines IL-1β, TNF-α, and IL-1Ra was examined in macrophages exposed to nanoparticles. SiO₂ nanoparticles strongly biased naïve macrophages towards inflam-mation (M1 polarisation), by selectively inducing production of inflammatory cytokines IL-1β and TNF-α. SiO₂ nanoparticles also significantly amplified the inflammatory phenotype of LPS-polarised M1 macrophages. Other ceramic nanoparticles had little influence on cytokine production, either in resting macrophages, or in LPS-activated cells. Generally, Co nanoparticles had an overall pro-inflammatory effect on naïve macrophages, by reducing anti-inflammatory IL-1Ra and inducing inflammatory TNF-α. However, Co nanoparticles reduced production of IL-1β and IL-1Ra, but not TNF-α, in LPS-polarised M1 macrophages. Thus, exposure to different nanoparticles can modulate, in different ways, the defence/inflammatory capacities of macrophages. A thorough analysis of these biasing effects may shed light on the mechanisms of pathogensis of several diseases based on dysregulation of the immune response (allergies, autoimmunity, tumours).

---

Keywords

---