Titanium dioxide NOAA affect p38 MAPK mediated signaling pathway and stimulate phagocytic activity in the sea urchin immune cells

Nanotechnology is one of the most active research areas in our contemporary society. The presence of nano-objects and their aggregates and agglomerates (NOAA) in many consumer products has attracted a growing scientific concern on the possible effects of these materials on the environment and biota. Here, we took advantage of an amenable laboratory model organism, the sea urchin Paracentrotus lividus (phylum Echinodermata), to elucidate a potential pathway that can be involved in the persistent Titanium dioxide (TiO2) NOAA-immune cell interaction. Sea urchins are phylogenetically related to humans (at least 70% of their proteins are shared with humankind), and have been proven to posses a sophisticated and sensitive immune system. Their immune cells carry out functions similar to those of the vertebrates immune system homologs; phagocytes, are the most abundant type of immune cells present in the main body cavity fluid. In this study, TiO2 NOAA were injected into the sea urchins body cavity to expose immune cells, that were harvested after 24 hours, and analyzed for their morphology, phagocytic ability, activation of proteins triggering immune response (e.g. HSPs, TLRs, p38 MAPK) and expression of related immune response genes. We found that TiO2 NOAA elicit a receptor-mediated endocytotic mechanism carried out by phagocytes, involving the p38 MAPK signaling pathway. Our working hypothesis is based on the role of the TiO2 NOAA -mediated p38 MAPK inactivation in the renewal and homeostasis of sea urchin immune stem cells. In conclusion, we recommend sea urchin immune cells as a new powerful tool for nano-safety investigations.