Abstract
Many chronic diseases manifest in prolonged inflammation and often ignored dysregulated lipid metabolism. When associated with inhalation of nanomaterials, limited information is available on the relevant molecular events and their causal connections. This prevents reliable prediction of outcomes by efficient testing strategies. To unravel how acute nanomaterial exposure leads to chronic conditions, we employed advanced microscopy and omics in vitro and in vivo together with in silico modelling. For selected metal-oxide nanomaterials, we show that lung epithelial cells survive the exposure by excreting internalized nanomaterials and passivating them on the surface, employing elevated lipid synthesis. Macrophages, on the contrary, lose their integrity whilst degrading the passivized bio-nano agglomerates, releasing the nanomaterials, which are taken up again by the epithelial cells. Constant proinflammatory signalling recruits new phagocytes that feed the vicious cycle of events, resulting in a long-lasting response to a single exposure. The proposed mechanism explains the nanomaterial-associated in vivo chronic outcomes and allows its prediction based on in vitro measurements. Similar mechanisms may trigger other chronic diseases affecting millions of lives worldwide.
Footnotes
↵* Materials & Correspondence Materials and correspondence should be addressed to Hana Majaron, Boštjan Kokot or Aleksandar Sebastijanović
Title, text and figures were revised for clarity, author list was updated, and additional Supplementary information was added
http://lbfnanobiodatabase.ijs.si/file/data/cauliflowerpaper/