Attività emolitica e infiammatoria (inflammasoma) di quarzi sintetizzati in dimensione sub-micrometrica

The occupational exposure to quartz is known to induce severe detrimental effects and it has been shown that surface properties govern quartz toxicity (Fubini & Fenoglio, 2007). It is believed that the hazard posed by quartz dust varies from one to the other source as subtle alteration of the surface state modulates toxicity (Donaldson & Borm, 1998; Fubini, 1998). So far, all toxicological studies have been carried out on quartz dust obtained from fragmentation. No data are available on dust made up of submicron size as crystallized quartz crystals, where the reactivity associated to fractured surface is absent. In order to assess the toxicity of quartz as prepared, a novel synthetic pathway to crystalline silica is proposed and a set of micro and nano quartz sample have been produced and studied. This new method of synhesis allows to reach higher supersaturation values with respect to the solubility of silica in water or in alkaline solution. The Na-metasilicate solution was polymerized adding different polymerizing agents (HCl, HNO3, CO2). All samples show good crystallinity from XRPD experiment. A systematic interlaboratory study, on the reactivity of these recently synthesized high pure nanocrystalline quartz was performed. In order to connect some key to toxicity-relevant features, including size/surface and crystalline properties the samples were tested in Hemolysis. The hemolytic model provides a measure of the direct particle surface/ membrane interaction, thus allowing to exclude other variables different from the surface property of silica particles. Free radical release, crystallinity, micromorphology are some of the inherent characteristics affecting silica surface which have been taken into account. Have been tested in hemolysis also the inhibitory potential of Carbon-loaded quartz, as validation of the decreasing in pathogenic potential of carbon in coal mine dust.With hemolysis have been finally tested the interaction of silica with erythrocyte ghost membrane with consequent decreasing of hemolytic activity of quartz pre-incubated with ghost membranes. After a first determination of the hemolytic activity, a correlation was considered with other biological events implicated in the pathogenesis of silicosis, such as the pro-inflammatory response and fibrosis. While for the latter a relationship is unlikely, the activation of the inflammasome Nalp3, identified as responsible of the silica-induced inflammatory pathway through interleukin IL-1β release, has proved likely correlated to the hemolytic potential. These findings suggest a possible role of the same physico-chemical properties involved in hemolysis even for the Nalp3 inflammasome recruitment, which seems in turn to be another subordinate to the variability of quartz.