Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages.
Kupffer cells form a large intravascular macrophage bed in the liver sinusoids. The differentiation history and diversity of Kupffer cells is disputed; some studies argue that they are derived from blood monocytes, whereas others support a local origin from intrahepatic precursor cells. In the present study, we used both flow cytometry and immunohistochemistry to distinguish 2 subsets of Kupffer cells that were revealed in the context both of bone marrow transplantation and of orthotopic liver transplantation. One subset was radiosensitive and rapidly replaced from hematogenous precursors, whereas the other was relatively radioresistant and long-lived. Both were phagocytic but only the former population was recruited into inflammatory foci in response to CD8(+) T-cell activation. We propose the name "sessile" for the radioresistant Kupffer cells that do not participate in immunoinflammatory reactions. However, we found no evidence that these sessile Kupffer cells arise from immature intrahepatic precursors. Our conclusions resolve a long-standing controversy and explain how different experimental approaches may reveal one or both of these subsets.
Klein
Ingo
I
David H Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester School of Medicine and Dentistry, NY, USA. klein_i@chirurgie.uni-wuerzburg.de
Cornejo
Judith C
JC
Polakos
Noelle K
NK
John
Beena
B
Wuensch
Sherry A
SA
Topham
David J
DJ
Pierce
Robert H
RH
Crispe
Ian Nicholas
IN
D000818:Animals; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007728:Kupffer Cells / Q000166:cytology* / Q000276:immunology; D008099:Liver / Q000166:cytology* / Q000276:immunology; D016031:Liver Transplantation; D008213:Lymphocyte Activation / Q000276:immunology / Q000528:radiation effects; D008262:Macrophage Activation / Q000528:radiation effects; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D014916:Whole-Body Irradiation
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