Biotransformation of soluble-insoluble lanthanum species and its induced NLRP3 inflammasome activation and chronic fibrosis.

Soluble lanthanum (La)(Ⅲ) species that have been extensively used as fertilizers in agriculture can potentially get into the human body through foods and environment. Most soluble La(Ⅲ) species can rapidly transform into insoluble La(Ⅲ) species under physiological conditions, however, their potential biological behavior and chronic toxicity are rarely investigated. In the present study, insoluble La(Ⅲ) species formed under physiological condition were identified as nanoscale or microscale particles, and their major components were found to experience biotransformation process upon contact with cells. Insoluble La(Ⅲ) species could adhere to extracellular membrane or be internalized into cells, capable of activating a nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. The underlying mechanism could be ascribed to K+ efflux and lysosomal rupture because these insoluble La(Ⅲ) species locating at extracellular membrane could reduce the unsaturated fatty acids of cell membrane, leading to potassium (K+) efflux, and those internalized into cells could consume the phospholipids of lysosomal membrane, leading to lysosomal rupture. Mice daily drinking soluble La(Ⅲ) species to mimic drinking tea process for 90 days were found to present NLRP3 inflammasome activation in liver and kidney, as a result of chronic fibrosis, which is potentially correlated to insoluble La(Ⅲ) species formation.