Cross-activating invariant NKT cells and kupffer cells suppress cholestatic liver injury in a mouse model of biliary obstruction
| Autor: | Eric P. Sun, Nico van Rooijen, Caroline C. Duwaerts, Stephen H. Gregory, Chao Wen Cheng |
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| Přispěvatelé: | Molecular cell biology and Immunology, CCA - Immuno-pathogenesis |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Necrosis
Kupffer Cells Cell Nitric Oxide Synthase Type II lcsh:Medicine Biology Lymphocyte Activation Real-Time Polymerase Chain Reaction digestive system Flow cytometry Nitric oxide 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals lcsh:Science 030304 developmental biology Liver injury 0303 health sciences Multidisciplinary Cholestasis medicine.diagnostic_test Kupffer cell lcsh:R medicine.disease Natural killer T cell Flow Cytometry Molecular biology Nitric oxide synthase Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure chemistry Liver 030220 oncology & carcinogenesis Immunology biology.protein Natural Killer T-Cells Female lcsh:Q medicine.symptom Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 11, p e79702 (2013) PLoS ONE Duwaerts, C C, Sun, E P, Cheng, C W, van Rooijen, N & Gregory, S H 2013, ' Cross-Activating Invariant NKT Cells and Kupffer Cells Suppress Cholestatic Liver Injury in a Mouse Model of Biliary Obstruction ', PLoS ONE, vol. 8, no. 11, e79702 . https://doi.org/10.1371/journal.pone.0079702 PLoS ONE, 8(11):e79702. Public Library of Science |
| ISSN: | 1932-6203 |
| Popis: | Both Kupffer cells and invariant natural killer T (iNKT) cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry), mRNA expression (qtPCR), nitric oxide (NO (.) ) production (Griess reaction), and protein secretion (cytometric bead-array or ELISAs) were determined. To address the potential role of NO (.) in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS) inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA)-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO (.) , and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury. |
| Databáze: | OpenAIRE |
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