Abstract
Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation.
Highlights
Kupffer cells (KCs) are liver resident macrophages which represent the largest population of macrophages in the body, constituting approximately 10% of all hepatic cells and approximately 80% of the tissue macrophages, including alveolar, splenic, and peritoneal macrophages [1]
We examined the role of Kupffer cells in local, systemic, acute, and chronic inflammation models and indicate that Kupffer cells are involved in the pathogenesis of collagen-induced arthritis as a model of chronic, systemic inflammation
The population of KCs was expressed as F4/80+CD11bmiddle+ group (Figure 1(a)) and the population was completely deleted by clodronate-liposome administration for 5 days after treatment and gradually restored from 7 to 9 days (Figure 1(a))
Summary
Kupffer cells (KCs) are liver resident macrophages which represent the largest population of macrophages in the body, constituting approximately 10% of all hepatic cells and approximately 80% of the tissue macrophages, including alveolar, splenic, and peritoneal macrophages [1]. The functions have been extensively investigated, especially (and naturally) in the field of liver inflammation [8,9,10,11,12,13,14] For these studies, one important finding by Van Rooijen and Sanders was the key triggering method that intravenous administration of clodronatecontaining liposomes deletes spleen and liver but not other tissue resident macrophages [15]. The attention of the researchers have been restricted only to the functions of Kupffer cells in the specific local site, liver We speculated that this largest population of tissue macrophages has influence on systemic inflammation in some way. We examined the role of Kupffer cells in local, systemic, acute, and chronic inflammation models and indicate that Kupffer cells are involved in the pathogenesis of collagen-induced arthritis as a model of chronic, systemic inflammation
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