Formyl-Peptide Receptor Agonists and Amorphous SiO(2)-NPs Synergistically and Selectively Increase the Inflammatory Responses of Human Monocytes and PMNs

We tested whether amorphous SiO(2)-NPs and formylpeptide receptor (FPRs) agonists synergistically activate human monocytes and neutrophil polymorphonuclear granulocytes (PMNs). Peptide ligands specifically binding to FPR1 (f-MLP) and to FPR2 (MMK-1, WKYMVM and WKYMVm) human isoforms did not modify the association of SiO(2)-NPs to both cell types or their cytotoxic effects. Similarly, the extent of CD80, CD86, CD83, ICAM-1 and MHCII expression in monocytes treated with SiO(2)-NPs was not significantly altered by any FPRs agonist. However, FPR1 stimulation with f-MLP strongly increased the secretion of IL-1β, IL-6 and IL-8 by human monocytes, and of IL-8 by PMNs in the presence of SiO(2)-NPs, due to the synergic stimulation of gene transcription. FPR2 agonists also up-modulated the production of IL-1β induced by monocytes treated with SiO(2)-NPs. In turn, SiO(2)-NPs increased the chemotaxis of PMNs toward FPR1-specific ligands, but not toward FPR2-specific ones. Conversely, the chemotaxis of monocytes toward FPR2-specific peptides was inhibited by SiO(2)-NPs. NADPH-oxidase activation triggered by FPR1- and FPR2-specific ligands in both cell types was not altered by SiO(2)-NPs. Microbial and tissue danger signals sensed by FPRs selectively amplified the functional responses of monocytes and PMN(S) to SiO(2)-NPs, and should be carefully considered in the assessment of the risk associated with nanoparticle exposure.