Introduction: Further knowledge of basic mechanisms that regulate liver regeneration may help to find therapies to increase otherwise insufficient liver mass. The chemokine receptor CCR5 is an important player in the trafficking of macrophages. As macrophages are strongly involved in liver regeneration we investigated the role of CCR5 in liver regeneration. Methods: We performed a 70% hepatectomy in CCR5 knock-out (KO) and wild-type (wt) mice. Liver tissue was collected at various time points and analyzed for hepatocyte proliferation by immunostaining for Ki67 and for presence of macrophages by immunostaining for IBA1. Protein extracts were analyzed by Western blotting against proliferating cell nuclear antigen (PCNA). TNFalpha and IL-6 levels were analyzed in liver tissues by RT-PCR. We further screened sera for cytokines using Bioplex analyzis. Results: Immunostaining on liver sections showed an increased number of proliferating hepatocytes in CCR5 KO (41.6% ± 9.4) mice compared to wt mice (11.3% ± 6.9) at 48h. Western blotting against PCNA confirmed this result. The number of macrophages at 48h was increased in wt mice (54.9% ± 3.2) compared to KO mice (31.5%±3.8). Serum levels of TNFalpha and its expression in the liver are increased at 48h and 24h respectively in the wt compared to KO mice. No significant difference was observed for IL-6. Further, screening revealed increased blood levels for VEGF at 48h in KO mice and increased levels for MIP1alpha in wt mice. Conclusion: In hepatectomized CCR5KO mice liver regeneration is accelerated compared to wild-type mice. TNFalpha expression as well as number of Kupffer cells are decreased in CCR5 KO mice. Further investigations are needed to determine how the modified inflammatory events in CCR5 KO mice lead to increased hepatocyte proliferation.
To cite this abstract in AMA style:Gonelle-Gispert C, Sorce S, Morel P, Meier R, Lacotte S, Bosco D, Buhler L. Enhanced Liver Regeneration in Mice Lacking the Chemokine Receptor CCR5 [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/enhanced-liver-regeneration-in-mice-lacking-the-chemokine-receptor-ccr5/. Accessed May 5, 2021.
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