Chronic exposure of the RAW246.7 macrophage cell line to H2O2 leads to increased catalase expression

Abstract

Altered cellular redox states have been associated with a variety of chronic diseases, especially those correlated with inflammation. One of the primary oxidants generated during the inflammatory response is hydrogen peroxide (H₂O₂). Macrophages in particular are thought to produce large amounts of H₂O₂, however they must somehow protect themselves from the potentially lethal concentrations they produce. To investigate how immune cells protect themselves from H₂O₂ observed in chronic inflammatory diseases, we established an adapted population of macrophages in culture by gradually increasing sub-lethal concentrations of H₂O₂ in the media to typically lethal concentrations over the course of more than a month. The resulting cells were tolerant to very high concentrations of H₂O₂. Further investigation revealed that the cells were able to rapidly neutralize the H₂O₂ added to their culture media due to a dramatic upregulation of catalase. Interestingly, T cells, which are also implicated in chronic inflammation, were unable to adapt to H₂O₂ under the same procedure, however when T cells were cultured in media from adapted macrophages, they were able to survive typically lethal concentrations of H₂O₂. These data support the hypothesis that macrophages are able to protect themselves and neighboring cells during states of chronic inflammation from the oxidizing environment they create.

Keywords: Catalase; Cellular adaptation; Hydrogen peroxide; Inflammation; Oxidation.