Why does the hemolytic activity of XXXX predict its pro-inflammatory activity?

@entity82 @entity55 @entity19 @entity635 @entity19292 @entity3440 @entity2142
BACKGROUND: The hemolytic activity of inhaled particles such as @entity3440 has been widely investigated in the past and represents a usual toxicological endpoint to characterize particle reactivity despite the fact that red blood cells (RBCs) are not involved in the pathogenesis of @entity55 or @entity82 caused by some inhaled particles. The inflammatory process induced by @entity3440 starts with the activation of the inflammasome, which leads to the release of mature @entity635 . One of the upstream mechanisms causing activation of the inflammasome is the labilization of the phagolysosomal membrane after particle phagocytosis. Considering RBC lysis as a model of membrane damage, we evaluated the relationship between hemolytic activity and inflammasome-dependent release of @entity635 for a panel of selected @entity3440 particles, in search of the toxicological significance of the hemolytic activity of an inhaled particle. METHODS: Well-characterized @entity3440 particles, including four quartz samples and a vitreous @entity3440 , with different surface properties and hemolytic potential were tested for their capacity to induce inflammasome-dependent release of @entity635 in LPS-primed primary @entity19 peritoneal macrophages by ELISA and Western blot analysis. The mechanisms of @entity635 maturation and release were clarified by using ASC-deficient cells and inhibitors of phagocytosis and @entity19292 . RESULTS: The @entity3440 samples induced dose-dependent @entity2142 and @entity635 release of different amplitudes. A significant correlation between @entity635 release and hemolytic activity was evidenced (r   =   0.827) by linear regression analysis. @entity635 release was completely abolished in ASC-deficient cells and reduced by inhibitors, confirming the involvement of the inflammasome and the requirement of phagocytosis and @entity19292 for activation. CONCLUSIONS: The same physico-chemical properties of @entity3440 particles which are relevant for the lysis of the RBC membrane also appear implicated in the labilization of the phagolysosome, leading to inflammasome activation and release of the pro-inflammatory cytokine @entity635 . These findings strengthen the relevance of the @entity2142 assay to predict the pro-inflammatory activity of @entity3440 dusts.
