Abstract

Gastrointestinal exposure to nanoparticles and microparticles appears to be a normal occurrence and, likely, is something that humans have faced throughout evolution. In fact mechanisms have evolved to utilise, beneficially, at least one dietary nanoparticle, namely ferritin. This is the storage form of iron and is ingested in both the meat-based and plant-based aspects of the diet. Additionally, however, we propose that beneficial nano/microparticles may actively from in situ in the gut lumen. Of special note is calcium phosphate. The secretion of calcium and phosphate ions in the succus entericus (gut secretion fluid) leads to co-precipitation of particles. These could trap organic luminal molecules and then cross the epithelial barrier, especially at the M cell portal, as an entire conjugate. Cellular dissolution of the conjugate would release calcium ions and phosphate ions as well as the organic molecules (typically antigens) being carried and thus allow the immune system to survey the luminal contents. Our group is working to prove this hypothesis. Additionally, however, the M cell portal will be exposed to man-made particles such as silicates and titanium dioxide that enter the diet through ingestion of processed foods, pharmaceuticals, nutraceuticals and toothpaste. These particles are scavenged- probably via the mechanism intended for endogenously forming calcium phosphate- and can be seen to accumulate in the cells (macrophages) at the base of human intestinal lymphoid aggregates. They are likely to also adsorb to their surface luminal organic molecules, which they may subsequently release following cellular uptake. But unlike calcium phosphate, these man-made exogenous particles will not dissolve in the cell lysosome. So whether they then provide aggressive, persistent signals for cellular responses remains to be elucidated. Again, our group has a particular interest in the idea that certain genetically-susceptible individuals may have pro-inflammatory responses to these exogenous particles.

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