Cerium dioxide nanoparticles selectively up-regulate C-C chemokine receptor 2 and CD16 expression on human monocytes

Abstract

Cerium dioxide nanoparticles (CeO2 NPs) are known as scavengers of reactive oxygen species for the coexistence of Ce 3+ / Ce 4+ oxidation states. Cell treatments with CeO2 NPs often lead to controversial proinflammatory and anti-inflammatory results. The aim of the study was to investigate the immune events following the administration of ceria nanoparticles to THP-1 monocytes. To address this issue, we performed flow cytometry, chemotaxis and ELISA experiments on THP-1 monocytes treated with different concentrations of CeO2 NPs. CeO2 nanoparticle treatments induced a significant pro-inflammatory C-C chemokine receptor 2 (CCR2) up-regulation within the first 6 hours lasting over-expressed for 24 hours. Differently, CCR5 showed no response at any concentration tested. Enhanced chemotaxis towards the CCR2 specific ligand MCP-1 reinforced the observation demonstrating a functional immune outcome. The pro-inflammatory profile of the treated monocytes was also supported by CD16 upregulation but no differences in CX3CR1 or other monocyte receptors, like CD11b and CD14, were detectable. Moreover, CeO2 NPs exposure did not promote any release of inflammatory cytokines suggesting a specific and direct effect of the nanoparticles on CCR2 and CD16.Our in vitro results reveal a specific role of CeO2 NPs in the upregulation of CCR2, which might contribute to increase the proinflammatory monocyte/macrophage migration toward the sites of CCL2 expression.

Chemokines and nanomaterials: interaction for useful immune-applications

“…Indeed, recent observations with gold nanoparticles (AuNPs) reported that these particles phagocytized by immune cells can retard the sensitivity of some immune responses [92]. This is not true for all NPs, in fact, some NMs have been proved not only to release inflammatory mediators including chemokines, but also to stimulate the up-regulation of particular chemokine receptors involved in many processes of inflammation [93].…”

Metallic Nanoparticles: General Research Approaches to Immunological Characterization

“…Multiple-parameter analysis can also be performed using multiplex systems [ 88 , 108 , 109 ]. Cytokine release represents a key activity of immune cell to coordinate either inflammatory or anti-inflammatory responses.…”

“…Along with these well-known markers, the expression of membrane receptors involved in the cellular immune response can give the researcher important information [ 88 , 108 ]. Membrane proteins, as well as lipids, denote the activity of cells in the different physiological or pathological conditions.…”