An Eye on Kupffer Cells: Development, Phenotype and the Macrophage Niche

Abstract

Macrophages are key participants in the maintenance of tissue homeostasis under normal and pathological conditions, and implement a rich diversity of functions. The largest population of resident tissue macrophages is found in the liver. Hepatic macrophages, termed Kupffer cells, are involved in the regulation of multiple liver functionalities. Specific differentiation profiles and functional activities of tissue macrophages have been attributed to the shaping role of the so-called tissue niche microenvironments. The fundamental macrophage niche concept was lately shaken by a flood of new data, leading to a revision and substantial update of the concept, which constitutes the main focus of this review. The macrophage community discusses contemporary evidence on the developmental origins of resident macrophages, notably Kupffer cells and the issues of heterogeneity of the hepatic macrophage populations, as well as the roles of proliferation, cell death and migration processes in the maintenance of macrophage populations of the liver. Special consideration is given to interactions of Kupffer cells with other local cell lineages, including Ito cells, sinusoidal endothelium and hepatocytes, which participate in the maintenance of their phenotypical and functional identity.

Bioresponsive Chimaeric Polymersomes Mediate Sustained and Liver-Specific siRNA Transfection In Vivo

“…Flow cytometry analysis results of the sorted liver cells displayed that the percentage of nonparenchymal cells (mainly Kupffer cells) that internalized with siApoB (Cy5) was much higher than that of hepatocytes (6.13 vs 1.12%) (Figure D). Hepatocytes accounting for 60–70% of the total liver cells and Kupffer cells accounting for 10–15% of the total liver cells , are the major cells for the internalization of nanoparticles. , This indicates that approximately half of the BCP- siApoB can be taken up by hepatocytes and the other half by Kupffer cells. Besides, to study the distribution of BCP- siApoB (Cy5) in the liver, the tissue slices were stained with fluorescent dyes.…”

The impact of hepatocyte-specific deletion of hypoxia-inducible factors on the development of polymicrobial sepsis with focus on GR and PPARα function

“…Either, HIF factors are activated in hepatocytes, but play no mechanistic role in sepsis, or the transcriptional signals and reporter activities that were observed in the liver were from cells other that hepatocytes. Next to hepatocytes, which form 70% of the cells in the liver, 10% of the liver cells are Kupffer cells (KCs) ( 60 ). Also liver sinusoidal endothelial cells (LSECs, 15%) and hepatic stellate cells (HSCs, 5%) cooperate to shape and maintain liver function ( 61 ) and could thus be involved in the HIF activity observed in the liver during sepsis.…”

Angiocrine Signaling in Sinusoidal Health and Disease

“…LSECs, macrophages, and HSCs significantly contribute in the process of liver regeneration, 5 6 9 10 12 18 22 28 32 33 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 supported by scRNAseq and spatial transcriptomics studies. 55 Regeneration is studied via acute injury models such as the two-thirds partial hepatectomy model (PHx) 10 resulting in rapid regeneration of liver mass by 96 hours postinjury or the centrilobular necrosis with acetaminophen overdose (APAP) 38 (further discussed later).…”

“…LSECs, macrophages, and HSCs significantly contribute in the process of liver regeneration, 5,6,9,10,12,18,22,28,32,33,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] supported by scRNAseq and spatial transcriptomics studies. 55 Regeneration is studied via acute injury models such as the two-thirds partial hepatectomy model (PHx) 10 resulting in rapid regeneration of liver mass by 96 hours postinjury or the centrilobular necrosis with acetaminophen overdose (APAP) 38 (further discussed later).…”