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Impact of NKT Cells and LFA-1 on Liver Regeneration under Subseptic Conditions
- Source :
- PLoS ONE, PLoS ONE, Vol 11, Iss 12, p e0168001 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science, 2016.
-
Abstract
- Background Activation of the immune system in terms of subseptic conditions during liver regeneration is of paramount clinical importance. However, little is known about molecular mechanisms and their mediators that control hepatocyte proliferation. We sought to determine the functional role of immune cells, especially NKT cells, in response to partial hepatectomy (PH), and to uncover the impact of the integrin lymphocyte function-associated antigen-1 (LFA-1) on liver regeneration in a subseptic setting. Methods Wild-type (WT) and LFA-1-/- mice underwent a 2/3 PH and low-dose lipopolysaccharid (LPS) application. Hepatocyte proliferation, immune cell infiltration, and cytokine profile in the liver parenchyma were determined. Results Low-dose LPS application after PH results in a significant delay of liver regeneration between 48h and 72h, which is associated with a reduced number of CD3+ cells within the regenerating liver. In absence of LFA-1, an impaired regenerative capacity was observed under low-dose LPS application. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of NKT cell related cytokines IL-12 and IL-23 were expressed in the regenerating liver of LFA-1-/- mice, while the expression of NK cell-associated CCL5 and IL-10 was increased compared to WT mice. Conclusion A subseptic situation negatively alters hepatocyte proliferation. Within this scenario, we suggest an important impact of NKT cells and postulate a critical function for LFA-1 during processes of liver regeneration.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Physiology
Neutrophils
Lymphocyte
lcsh:Medicine
Partial Hepatectomy
NK cells
Pathology and Laboratory Medicine
White Blood Cells
Mice
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Morphogenesis
Lymphocyte function-associated antigen 1
Phosphorylation
lcsh:Science
Immune Response
Cells, Cultured
Innate Immune System
Multidisciplinary
Chemistry
T Cells
hemic and immune systems
Natural killer T cell
Liver regeneration
Lymphocyte Function-Associated Antigen-1
ddc
Cell biology
medicine.anatomical_structure
Liver
Hepatocyte
Cytokines
030211 gastroenterology & hepatology
medicine.symptom
Cellular Types
Anatomy
Research Article
STAT3 Transcription Factor
Immune Cells
Immunology
Inflammation
chemical and pharmacologic phenomena
Surgical and Invasive Medical Procedures
CCL5
03 medical and health sciences
Digestive System Procedures
Immune system
Signs and Symptoms
Diagnostic Medicine
medicine
Regeneration
Hepatectomy
Animals
Parenchymal Tissue
Blood Cells
Interleukin-6
lcsh:R
Biology and Life Sciences
Cell Biology
Molecular Development
Liver Regeneration
Mice, Inbred C57BL
030104 developmental biology
Suppressor of Cytokine Signaling 3 Protein
Immune System
Hepatocytes
Natural Killer T-Cells
lcsh:Q
Organism Development
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....39590c992e7a0abfaf7f632639b5d30a