Macrophages are essential for lymphocyte infiltration in formyl peptide-induced cholangitis in rat liver


Motoyasu Ishii, M.D., Third Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan


Abstract: 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.