The perfluoalkyl substance (PFASs) perfluorooctane sulfonate (PFOS) has been widely used in industry. However, PFOS is a persistent organic pollutant and has been gradually replaced by its short-chain analogs, perfluorohexane sulfonate (PFHxS) and perfluorobutane sulfonate (PFBS). PFASs are extremely persistent and are very frequently detected among the general population. The aim of the study was to determine the effect of selected PFASs on peripheral blood mononuclear cells (PBMCs) and the mechanisms of their action. PBMCs were exposed to PFOS, PFBS and PFHxS at concentrations ranging from 0.02 to 400 μM for 24 h, they were then tested for viability, apoptosis (changes in cytosolic calcium ions level and caspase-3, -8 and -9 activation), ferroptosis (changes in chelatable iron ions level and lipid peroxidation), and autophagy (LC3-II and Raptor level assay). PFOS exposure decreased cell viability, increased calcium ion level and caspase-8 activation; it also enhanced lipid peroxidation and increased the intracellular pool of chelatable iron ions as well as LC3-II protein content. In contrast, short-chain PFBS and PFHxS induced significant changes in the markers of apoptosis but had no substantial impact on ferroptosis or autophagy markers over a wide range of concentrations. Our results indicate that only PFOS demonstrated pro-ferroptotic and pro-autophagic potential but observed changes occurred at relatively high exposure. A short-chain substitute (PFBS) exhibited strong pro-apoptotic potential at concentrations related to occupational exposure. While the short-chain PFASs strongly affected the mitochondrial pathway of apoptosis, apoptosis itself was only induced by PFBS via the intrinsic and extrinsic pathways. It seems that the length of the carbon chain in PFASs appears to determine the cell death mechanisms activated in human PBMCs following exposure. Our findings provide a new insight into the immune toxicity mechanism induced by these compounds.
Keywords: Autophagy; Ferroptosis; PBMCs; PFOS; Perfluorooctane sulfonate.
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