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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4077-4085.
Prepublished online as a Blood First Edition Paper on August 9, 2007; DOI 10.1182/blood-2007-02-073841.
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Submitted February 12, 2007
Accepted July 25, 2007
Kupffer cell heterogeneity: functional properties of bone marrow-derived and sessile hepatic macrophages
Ingo Klein*, Judith C Cornejo, Noelle K Polakos, Beena John, Sherry A Wuensch, David J Topham, Robert H Pierce, and Ian Nicholas Crispe
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
Department of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
Department of General Surgery, University of Wurzburg, Wurzburg, Germany
* Corresponding author; email: klein_i{at}chirurgie.uni-wuerzburg.de.
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, while others support a local origin from intra-hepatic precursor cells. In the present study, we used both flow cytometry and immunohistochemistry to distinguish two subsets of Kupffer cells, which 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, while the other was relatively radio-resistant 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 radio-resistant Kupffer cells that do not participate in immuno-inflammatory reactions. However, we found no evidence that these sessile Kupffer cells arise from immature intra-hepatic precursors. Our conclusions resolve a long-standing controversy and explain how different experimental approaches may reveal one or both of these subsets.

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