Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle Exposure Is Size Specific

Abstract

The application of nanotechnology in the health care setting has many potential benefits; however, our understanding of the interactions between nanoparticles and our immune system remains incomplete. Although many of the biological effects of nanoparticles are negatively correlated with particle size, some are clearly size specific and the mechanisms underlying these size-specific biological effects remain unknown. Here, we examined the pro-inflammatory effects of silica particles in THP-1 cells with respect to particle size; a large overall size range with narrow intervals between particle diameters (particle diameter: 10, 30, 50, 70, 100, 300, and 1,000 nm) was used. Secretion of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced by exposure to the silica particles had a bell-shaped distribution, where the maximal secretion was induced by silica nanoparticles with a diameter of 50 nm and particles with smaller or larger diameters had progressively less effect. We found that blockade of IL-1β secretion markedly inhibited TNF-α secretion, suggesting that IL-1β is upstream of TNF-α in the inflammatory cascade induced by exposure to silica particles, and that the induction of IL-1β secretion was dependent on both the NLRP3 inflammasome and on uptake of the silica particles into the cells via endocytosis. However, a quantitative analysis of silica particle uptake showed that IL-1β secretion was not correlated with the amount of silica particles taken up by the cells. Further investigation revealed that the induction of IL-1β secretion and uptake of silica nanoparticles with diameters of 50 or 100 nm, but not of 10 or 1,000 nm, was dependent on scavenger receptor (SR) A1. In addition, of the silica particles examined, only those with a diameter of 50 nm induced strong IL-1β secretion via activation of Mer receptor tyrosine kinase, a signal mediator of SR A1. Together, our results suggest that the SR A1-mediated pro-inflammatory response is dependent on ligand size and that both SR A1-mediated endocytosis and receptor-mediated signaling are required to produce the maximal pro-inflammatory response to exposure to silica particles.

Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides

“…Because particle size influences the competence of immune responses induced by vaccination, it must be considered when vaccine formulations are intended for intranasal immunization . It has been frequently reported that particle size influences immune responses . With regard to vaccine Ags, it has been noted that only particles in the nanometre range, that is of the size of viruses, can reach lymph nodes and directly interact with B cells, inducing potent immune responses .…”

“…With regard to vaccine Ags, it has been noted that only particles in the nanometre range, that is of the size of viruses, can reach lymph nodes and directly interact with B cells, inducing potent immune responses . Comparisons of silica nanoparticle vaccines that contained particles of different diameters demonstrated that particles of the most effective formulations were 30‐50 nm in diameter . Synthetic haemozoin preparations that comprised 50‐200‐nm particles exhibited a stronger adjuvant effect compared with preparations with larger (2‐20 μm) or smaller (<50 nm) particles .…”

“…47,48 It has been frequently reported that particle size influences immune responses. [48][49][50][51][52][53][54][55][56] With regard to vaccine Ags, it has been noted that only particles in the nanometre range, that is of the size of viruses, can reach lymph nodes and directly interact with B cells, inducing potent immune responses. 48,50 Comparisons of silica nanoparticle vaccines that contained particles of different diameters demonstrated that particles of the most effective formulations were 30-50 nm in diameter.…”

“…48,50 Comparisons of silica nanoparticle vaccines that contained particles of different diameters demonstrated that particles of the most effective formulations were 30-50 nm in diameter. 49,54,55 Synthetic haemozoin preparations that comprised 50-200-nm particles exhibited a stronger adjuvant effect compared with preparations with larger (2-20 μm) or smaller (<50 nm) particles. 51 As was noted in studies of poly(lactic-co-glycolic acid) (PLGA) particle vaccine, a decrease in the diameter of PLGA particles with co-encapsulated CpG and OVA from 7 μm to 300 nm led to an increase in the titres of OVA-specific IgG Ab.…”

Nanoparticle Technology for Respiratory Tract Mucosal Vaccine Delivery

“…The key components of natural and synthetic polymers had been clearly identified and all that was required were processes to allow the manufacture of nanoparticles. Since functionality of nanoparticles is often associated with smaller sizes a practical definition of 1-100 nm has been adopted widely but clearly the scientific definition is derived from fundamental length dimension of particles in sizes smaller than 1,000 nm (Commissioner O.o.t., 2014;Nishijima N. et al, 2017).…”