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

Background/Aims: Cholangitis in rats induced by N-formyl L-methionine L-leu cine L-tyrosine (fMLT) is characterized by infiltration of mononuclear cell s around bile ducts in portal tracts. Methods: We investigated the initial process in fMLT-induced cholangitis histochemically. Results: Administratio n of fMLT into the colons of adult male Wistar rats with acetate-induced co litis resulted in an infiltration of mostly macrophages and granulocytes in to 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 NET reaction also di sappeared from the bile duct cells. Administration of carrageenan, a potent inhibitor of macrophage function, resulted in a significant decrease in ly mphocyte 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 ar e necessary for the subsequent migration of T lymphocytes around the bile d ucts.