Invading macrophages play a major role in the liver progenitor cell response to chronic liver injury
MetadataShow full item record
Background & Aims: Although a strong association between liver progenitor cells (LPCs) and inflammation exists in many chronic liver diseases, the exact role of the immune system in LPC-mediated hepatic regeneration remains unclear. A number of pro-inflammatory factors were identified in cytokine knockout mice in which the LPC response was attenuated but neither the mechanism nor the producing cells are known. Methods: To identify the critical immune cells and cytokines required in the LPC response, we compared two diet-induced models of liver injury with two recently established transgenic models of immune-mediated hepatitis. Results: Despite severe inflammation being observed in all models, the generation of LPCs was highly dependent on the cause and kinetics of liver damage. The LPC response was associated with an increase of macrophages and CD8+ T cells but not natural killer cells. T cell-deficient mice were able to mount a LPC response, albeit delayed, suggesting that T cells are not essential. Mice mounting an LPC response showed elevated numbers of Kupffer cells and invading CX3CR1 highCCR2high macrophages secreting persistent high levels of tumour necrosis factor alpha (TNFa), a major cytokine involved in the LPC response. Conclusions: Liver macrophages are an important determinant of LPC expansion during liver regeneration in models of diet- and immune-mediated liver injury. Invading macrophages in particular provide pro-mitogenic cytokines such as TNFa that underpin the process. LPC themselves are a source of chemokines (CCL2, CX3CL1) that attract infiltrating macrophages. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Showing items related by title, author, creator and subject.
Gene microarray analyses of daboia russelli russelli daboiatoxin treatment of THP-1 human macrophages infected with burkholderia pseudomalleiPerumal Samy, R.; Manikandan, J.; Pachiappan, A.; Ooi, E.; Aw, L.; Stiles, B.; Franco, O.; Kandasamy, M.; Mathi, K.; Rane, G.; Siveen, K.; Arunachalam, C.; Zayed, M.; Alharbi, S.; Kumar, A.; Sethi, Gautam; Lim, L.; Chow, V. (2015)© 2015 Bentham Science Publishers. Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection ...
Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regenerationElsegood, Caryn; Chan, C.; Degli-Esposti, M.; Wikstrom, M.; Domenichini, A.; Lazarus, K.; van Rooijen, N.; Ganss, R.; Olynyk, John; Yeoh, G. (2015)Liver progenitor cells (LPCs) are necessary for repair in chronic liver disease because the remaining hepatocytes cannot replicate. However, LPC numbers also correlate with disease severity and hepatocellular carcinoma ...
Jackaman, Connie; Radley-Crabb, Hannah; Soffe, Z.; Shavlakadze, T.; Grounds, M.; Nelson, Delia (2013)Changes to innate cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), during aging in healthy or tumor-bearing hosts are not well understood. We compared macrophage subpopulations and MDSCs from healthy ...