Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages.
The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady-state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80(high)CD11b(low) cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL-10, low or undetectable levels of IL-12p40 and TNF, and up-regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL-12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady-state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.
Departments of Gastroenterology and Hepatology, University Medical Center, Rotterdam, The Netherlands.
Dowty
D
Movita
Kim
K
Kreefft
Paula
P
Biesta
Adri
A
van Oudenaren
Pieter J M
PJ
Leenen
Harry L A
HL
Janssen
Andre
A
Boonstra
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D002478:Cells, Cultured; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007728:Kupffer Cells / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000276:immunology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D053592:Interleukin-1 Receptor-Associated Kinases; D016753:Interleukin-10; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C485837:Tollip protein, mouse; C507772:Irak3 protein, mouse