Related Experiment Videos
Macrophages are essential for lymphocyte infiltration in formyl peptide-induced cholangitis in rat liver
1Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Background/Aims:
Cholangitis in rats induced by N-formyl L-methionine L-leucine L-tyrosine (fMLT) is characterized by infiltration of mononuclear cells around bile ducts in portal tracts.
Methods:
We investigated the initial process in fMLT-induced cholangitis histochemically.
Results:
Administration of fMLT into the colons of adult male Wistar rats with acetate-induced colitis resulted in an infiltration of mostly macrophages and granulocytes into the portal tracts on day 1. Abnormal peroxidation as demonstrated by the nitro blue tetrazolium (NBT) reaction occurred in bile duct cells as well, although no apparent necrosis of the bile duct cells was observed. On day 4, the majority of the inflammatory cells in the portal tracts were CD4+ or CD8+ T lymphocytes. The oxidative products of the NBT reaction also disappeared from the bile duct cells. Administration of carrageenan, a potent inhibitor of macrophage function, resulted in a significant decrease in lymphocyte infiltration into the portal tracts. On day 8, portal inflammation subsided.
Conclusions:
In formyl peptide-induced cholangitis, macrophages and granulocytes may injure bile ducts transiently. Further, macrophages are necessary for the subsequent migration of T lymphocytes around the bile ducts.
Insights
N-formyl L-methionine L-leucine L-tyrosine (fMLT)-induced cholangitis in rats involves initial macrophage and granulocyte infiltration, potentially causing transient bile duct injury. Macrophages are crucial for subsequent T lymphocyte migration, resolving inflammation.
Area of Science:
- Gastroenterology and Hepatology
- Immunology
- Cell Biology
Background:
- Cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine (fMLT) in rats is characterized by mononuclear cell infiltration around bile ducts.
- Understanding the initial cellular events in fMLT-induced cholangitis is crucial for deciphering its pathogenesis.
Purpose of the Study:
- To investigate the initial cellular and molecular processes in fMLT-induced cholangitis.
- To elucidate the role of different immune cells in the development and resolution of cholangitis.
Main Methods:
- Histochemical analysis of fMLT-induced cholangitis in Wistar rats.
- Assessment of cellular infiltration (macrophages, granulocytes, T lymphocytes) and oxidative stress (nitro blue tetrazolium reaction).
- Evaluation of the effect of carrageenan (macrophage inhibitor) on lymphocyte infiltration.
Main Results:
- fMLT administration led to rapid infiltration of macrophages and granulocytes into portal tracts, with abnormal peroxidation in bile duct cells.
- CD4+ and CD8+ T lymphocytes became predominant by day 4, coinciding with the disappearance of oxidative products.
- Carrageenan treatment significantly reduced lymphocyte infiltration, indicating a critical role for macrophages in T cell recruitment.
Conclusions:
- Macrophages and granulocytes may cause transient injury to bile ducts in fMLT-induced cholangitis.
- Macrophages are essential for the subsequent recruitment of T lymphocytes to the peribiliary area.
- The study highlights a sequential immune cell involvement in the pathogenesis and resolution of experimental cholangitis.