SARS-CoV-2 infection induces expression and secretion of lipocalin-2 and regulates iron in a human lung cancer xenograft model
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defenseagainst bacterial infections through iron sequestration, and itserves as a biomarker for kidney injury. In a human protein array,we observed increased lipocalin-2 expression due to parentalSARS-CoV-2 infection in the Calu-3 human lung cancer cellline. The secretion of lipocalin-2 was also elevated in responseto parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha,Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression andsecretion. Additionally, the iron concentration increased in theCalu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the productionand secretion of lipocalin-2, potentially resulting in a decreasein iron concentration in serum. Because the concentrationof iron ions in the blood is associated with anemia, this phenomenoncould contribute to developing anemia in COVID-19patients.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defenseagainst bacterial infections through iron sequestration, and itserves as a biomarker for kidney injury. In a human protein array,we observed increased lipocalin-2 expression due to parentalSARS-CoV-2 infection in the Calu-3 human lung cancer cellline. The secretion of lipocalin-2 was also elevated in responseto parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha,Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression andsecretion. Additionally, the iron concentration increased in theCalu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the productionand secretion of lipocalin-2, potentially resulting in a decreasein iron concentration in serum. Because the concentrationof iron ions in the blood is associated with anemia, this phenomenoncould contribute to developing anemia in COVID-19patients.
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