Bile acids induce eosinophil degranulation by two different mechanisms.
Eosinophil infiltration and activation occur in the vicinity of the bile ducts in immune cholangiopathies. When cholangiocytes are injured, bile acids may cross the damaged biliary epithelia and affect periductal immune cells. Although immunomodulatory actions of bile acids have been well explored, their effects on eosinophils have never been examined. In this study, we tested the hypothesis that bile acids directly activate eosinophils and induce their effector functions. We found that a hydrophobic bile acid, taurine-con- jugated chenodeoxycholic acid (TCDCA), induces eosinophil degranulation in vitro via 2 different mechanisms depending on its concentration. Degranulation induced by 100 to 500 micromol/L TCDCA was an active and regulated release because it was completely abolished by a tyrosine kinase inhibitor (genistein), by a microfilament inhibitor (cytochalasin B), and by incubation at 4 degrees C. Furthermore, eosinophils stimulated with 10 to 250 micromol/L TCDCA vigorously produced superoxide and interleukin-8 (IL-8). In contrast, at higher concentrations (e.g., > or = 1,000 micromol/L), TCDCA induced granule protein release without concomitant superoxide production and IL-8 production. Further genistein and cytochalasin B failed to inhibit eosinophil degranulation induced by 2,500 micromol/L TCDCA, suggesting that TCDCA at this concentration induced passive degranulation via cytolysis. The analyses of cell morphology and functional viability also supported the presence of 2 mechanisms for TCDCA-induced eosinophil degranulation. Taurine-conjugated ursodeoxycholic acid, a hydrophilic bile acid, similarly activated human eosinophils at relatively low concentrations, although the potency was always lower compared with that of TCDCA. In conclusion, we have shown that bile acids are capable of directly activating eosinophils.
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
K
K
Yamazaki
G J
GJ
Gleich
H
H
Kita
D015550:Cell Degranulation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D016209:Interleukin-8; D013481:Superoxides; D013655:Taurochenodeoxycholic Acid