TY - JOUR
T1 - Bile acids induce eosinophil degranulation by two different mechanisms
AU - Yamazaki, K.
AU - Gleich, G. J.
AU - Kita, H.
N1 - Funding Information:
Abbreviations: CDCA, unconjugated chenodeoxycholic acid; CMC, critical micellar concentration; DCS, defined calf serum; EDN, eosinophil-derived neurotoxin; GCDCA, glycine-conjugated chenodeoxycholic acid; GUDCA, glycine-conjugated ursodeoxycholic acid; HSA, human serum albumin; MACS, magnetic cell separation system; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethophenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; PBC, primary biliary cirrhosis; TCDCA, taurine-conjugated chenodeoxycholic acid; TUDCA, taurine-conjugated ursodeoxycholic acid; UDCA, unconjugated ursodeoxycholic acid. From the Departments of Immunology and Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN. Received August 17, 2000; accepted December 4, 2000. Supported by grants from the National Institutes of Health (AI 34486 and AI 34577), by Mitsubishi-Tokyo Pharmaceuticals Inc., and by the Mayo Foundation. Address reprint requests to: Hirohito Kita, M.D., Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905. E-mail: Kita.hirohito@mayo.edu; fax (507) 284-5045. Copyright © 2001 by the American Association for the Study of Liver Diseases. 0270-9139/01/3303-0014$35.00/0 doi:10.1053/jhep.2001.22168
PY - 2001
Y1 - 2001
N2 - 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-conjugated chenodeoxycholic acid (TCDCA), induces eosinophil degranulation in vitro via 2 different mechanisms depending on its concentration. Degranulation induced by 100 to 500 μmol/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°C. Furthermore, eosinophils stimulated with 10 to 250 μmol/L TCDCA vigorously produced superoxide and interleukin-8 (IL-8). In contrast, at higher concentrations (e.g., ≥ 1,000 μmol/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 μmol/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.
AB - 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-conjugated chenodeoxycholic acid (TCDCA), induces eosinophil degranulation in vitro via 2 different mechanisms depending on its concentration. Degranulation induced by 100 to 500 μmol/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°C. Furthermore, eosinophils stimulated with 10 to 250 μmol/L TCDCA vigorously produced superoxide and interleukin-8 (IL-8). In contrast, at higher concentrations (e.g., ≥ 1,000 μmol/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 μmol/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.
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U2 - 10.1053/jhep.2001.22168
DO - 10.1053/jhep.2001.22168
M3 - Article
C2 - 11230738
AN - SCOPUS:0035120816
SN - 0270-9139
VL - 33
SP - 582
EP - 590
JO - Hepatology
JF - Hepatology
IS - 3
ER -