Calciprotein particles (CPPs) are nanoparticles composed of calcium phosphate crystals and fetuin-A and have been implicated in diseases associated with inflammation. In the current study, we investigated the molecular mechanisms underlying CPP-induced inflammation in mice. CPPs predominantly upregulated IL-1b and IL-1a and provided priming and activation signals for the NLRP3 inflammasome in murine macrophages. Pharmacological and genetic inhibition of the NLRP3 inflammasome revealed that CPPs induced the release of IL-1b and IL-1a via NLRP3 inflammasome-dependent and -independent mechanisms, respectively. CPPs also induced necrotic cell death, but gasdermin D was dispensable for CPP-induced IL-1b release and necrotic cell death. Although phagocytosis of CPPs was required for CPP-induced IL-1b/a release and necrotic cell death, lysosomal dysfunction and K + efflux were mainly involved in CPP-induced NLRP3 inflammasome activation and subsequent IL-1b release but not in CPP-induced IL-1a release and necrotic cell death. In vivo experiments showed that CPP administration evoked acute inflammatory responses characterized by neutrophil accumulation via both IL-1b and IL-1a. In particular, CPPinduced neutrophil inflammation was mediated predominantly through an IL-1a-induced CXCL1/CXCR2 signaling pathway. These results provide new insights into the mechanism underlying CPP-induced inflammation and suggest that targeting both IL-1b and IL-1a is necessary to regulate the CPP-induced inflammatory response and to treat CPP-associated inflammatory disorders. ImmunoHorizons, 2021, 5: 602-614.

No abstract

No abstract

No abstract

Purpose There has been an increasing use of plastic motor car fuel tanks in recent decades with the expected benefits of lighter weight, shape flexibility and lower cost. In this paper, the environmental life cycle assessments of mild steel and high-density polyethylene (HDPE) car fuel tanks in Japan are compared for two cases, namely the current average processes (base case), and for the same processes with the maximum currently feasible pollution control technology installed. Materials and methods Primarily, data from Japan are used for a life cycle inventory analysis, followed by an impact assessment based on the Life Cycle Impact Assessment Method Based on Endpoint Modelling and five other indicators.Results and discussion Mild steel shows a notably higher inventory for resources iron, manganese, zinc, coking coal, combustion coal, dolomite, limestone; for the air pollutants nitrogen oxides (NOx) from mobile sources, PM 10 , sulphur dioxide, hydrocarbons; and for solid waste (slag). HDPE has a higher inventory for resources liquefied natural gas reserves, oil reserves, for the air pollutants carbon dioxide, NO x from non-mobile sources and sulphur oxides. The base case environmental impact assessment results for six indicators show HDPE and steel to have similar impacts for all but one of the indicators. With pollution control, the feasible reductions in respective pollutant inventories range from 0% to 97%, while the corresponding impact assessment shows indicator values reduced by 0% to 29%, with slightly improved performance of mild steel relative to HDPE.Conclusions Accounting for a 62-year period of use and recycling for the mild steel would show a further decrease in the impact of the mild steel relative to HDPE.