Chemotaxis of Kupffer Cells Isolated from Rodent Liver

Miyazaki, Kohji; Aso, Masakazu; Torisu, Motomichi

doi:10.1111/j.1348-0421.1981.tb00112.x

Cited by 3 publications

(1 citation statement)

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“…15,43 In the current study, splenic and hepatic MCP-1 and KC mRNA levels increased significantly following refrigerator storage-damaged RBC transfusions (Figure 4 Panels E–F); splenic up-regulation was more prominent, perhaps because there were more macrophages per gram of sample used for RNA isolation. 44–46 However, given the >10-fold size difference between liver and spleen, hepatic synthesis is also likely significant.…”

Section: Discussionmentioning

confidence: 99%

Macrophages clear refrigerator storage–damaged red blood cells and subsequently secrete cytokines in vivo, but not in vitro, in a murine model

et al. 2014

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BACKGROUND In mice, refrigerator-stored red blood cells (RBCs) are cleared by extravascular hemolysis and induce cytokine production. To enhance understanding of this phenomenon, we sought to model it in vitro. STUDY DESIGN AND METHODS Ingestion of refrigerator-stored murine RBCs and subsequent cytokine production were studied using J774A.1 mouse macrophage cells and primary murine splenic macrophages. Wild-type and Ccl2-GFP-reporter mice were used for RBC clearance in vivo. RESULTS Although J774A.1 cells and primary macrophages preferentially ingested refrigerator-stored RBCs in vitro, as compared to freshly-isolated RBCs, neither produced increased cytokines following erythrophagocytosis. In contrast, phagocytosis of refrigerator-stored RBCs in vivo induced increases in circulating monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC), and correspondingly increased mRNA levels in mouse spleen and liver. In the spleen, these were predominantly expressed by CD11b+ cells. Using Ccl2-GFP-reporter mice, the predominant splenic population responsible for MCP-1 mRNA production were tissue-resident macrophages (i.e., CD45+, CD11b+, F4/80+, Ly6c+, CD11clow cells). CONCLUSION J774A.1 cells and primary macrophages selectively ingested refrigerator-stored RBCs by phagocytosis. Although cytokine expression was not enhanced, this approach could be used to identify the relevant receptor-ligand combination(s). In contrast, cytokine levels increased following phagocytosis of refrigerator-stored RBCs in vivo. These were primarily cleared in the liver and spleen, which demonstrated increased MCP-1 and KC mRNA expression. Finally, in mouse spleen, tissue-resident macrophages were predominantly involved in MCP-1 mRNA production. The differences between cytokine production in vitro and in vivo are not yet well understood.

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