Irradiated and CCl4 -treated bone marrow-derived liver macrophages exhibit different gene expression patterns and phenotypes

Abstract

Myeloid cells infiltrate into the liver and differentiate into macrophages in different liver injury mouse models. However, the heterogeneity of bone marrow (BM)-derived LMs populations remains to be understood. To investigate this and understand the impact of the macrophage niche on the properties of recruited BM-derived macrophages, we used a non-myeloablation BM transplantation model to label and trace BM-derived LMs. Subsequently, we quantified the number of embryonic-derived liver-resident macrophages, BM-derived LMs and total LMs in CCl₄ and irradiated acute liver injury mouse models, respectively. Finally, we compared the cell fate, gene expression patterns, chemokine signals, and surface markers of irradiated and CCl₄ -treated BM-derived LMs. We observed that, as compared to CCl_4, radiation generated a macrophage niche by depleting embryonic-derived liver-resident macrophages and induced the recruitment of BM-derived LMs that further settled in the liver. Irradiated and CCl₄ -treated BM-derived LMs are different with respect to their cell fates, gene expression patterns, and chemokine expression and recruitment. They also have different surface markers shortly after differentiating from their progenitors. Our findings suggest that irradiated and CCl₄ -treated LM populations derived from the bone marrow display different patterns of gene expression and phenotypes; these differences may be due to the availability of macrophage niche.

Keywords: CCl4-recruited; bone marrow-derived liver macrophages; heterogeneity; macrophage niche; radiation-recruited.