Bile and bile salts potentiate superoxide anion release from activated, rat peritoneal neutrophils.
Bile and bile salts potentiate superoxide anion release from activated, rat peritoneal neutrophils.
复制标题
胆汁和胆盐可增强活化的大鼠腹膜中性粒细胞释放超氧阴离子。
DOI：
10.1016/s0041-008x(88)80010-3
复制
发表时间：
1988
影响因子：
3.8
通讯作者：
Roth,RA
中科院分区：
文献类型：
--
作者：
Dahm,LJ;Hewett,JA;Roth,RA
某些胆汁盐在给予动物时引起肝毒性以及肝外器官损伤。活化的中性粒细胞（PMN）可通过释放活性氧和其他产物引起组织损伤。由于中性粒细胞可能会接触胆汁成分，如胆汁盐，在化学损伤肝脏或胆汁淤积期间，我们研究了胆汁和胆汁盐刺激大鼠腹膜中性粒细胞释放超氧阴离子（O−2）的能力。除了石胆酸盐之外，胆汁和胆汁盐本身都不能刺激中性粒细胞释放O− 2。石胆酸盐（32 μM）引起中性粒细胞释放少量但具有统计学意义的O− 2。当中性粒细胞被12-O-十四烷酰基-佛波醇-13-乙酸酯（PMA）（一种中性粒细胞的经典刺激物）刺激时，加入胆汁和某些胆汁盐显著增强了中性粒细胞的O− 2释放。单羟基胆汁酸盐石胆酸盐对PMA致敏的PMN具有最大的刺激活性，导致O− 2释放增加约8倍。石胆酸盐在10 ~ 32 μM浓度范围内增强作用最大，从大鼠血液中分离的中性粒细胞也有这种增强作用。二羟基胆汁酸盐、脱氧胆酸盐和鹅脱氧胆酸盐（100 μM）可使致敏的PMN释放O− 2的能力适度增强（2 ~ 3倍）。胆酸盐，一种三羟基胆汁盐，在这些浓度下没有活性。将石胆酸盐或鹅去氧胆酸盐与甘氨酸或牛磺酸结合，可显著降低胆汁盐增强致敏PMN释放O− 2的能力。胆盐分子亲水侧链或平面疏水部分的结构改变降低了PMA致敏的PMN增强O− 2释放的能力。这些结果表明，胆盐可以增强中性粒细胞的呼吸爆发，并表明这种相互作用在以血清胆盐升高为特征的中毒或疾病状态中发挥作用。
Certain bile salts cause hepatotoxicity as well as injury to extrahepatic organs when administered to animals. Activated neutrophils (PMNs) may cause tissue injury by releasing reactive oxygen species and other products. Since PMNs may come in contact with biliary components, such as bile salts, following chemical insult to the liver or during cholestasis, we examined the capacity of bile and bile salts to stimulate superoxide anion (O−2) release from rat peritoneal PMNs in vitro. Neither bile nor bile salts, with the exception of lithocholate, could by themselves stimulate O−2release from PMNs. Lithocholate (32 μM) caused small but statistically significant release of O−2from PMNs. When PMNs were primed with a barely suprathreshold concentration of 12-O-tetradecanoyl-phorbol-13-acetate (PMA), a classic stimulus for PMNs, the addition of bile and certain bile salts markedly enhanced O−2release from PMNs. The monohydroxy bile salt, lithocholate, had the greatest stimulatory activity toward PMA-primed PMNs, causing approximately an eightfold increase in O−2release. The enhancing effect of lithocholate was maximal between 10 and 32 μM, and it also occurred with PMNs isolated from rat blood. Dihydroxy bile salts, deoxycholate and chenodeoxycholate (100 μM), caused more modest enhancement of O−2release (two- to threefold) from primed PMNs. Cholate, a trihydroxy bile salt, was not active at these concentrations. Conjugation of either lithocholate or chenodeoxycholate with either glycine or taurine markedly reduced the ability of the bile salt to enhance O−2release from primed PMNs. Structural alterations on the hydrophilic side chain or within the planar, hydrophobic portion of the bile salt molecule reduced the capacity to enhance O−2release from PMA-primed PMNs. These results indicate that bile salts can potentiate the respiratory burst in PMNs and suggest a role for this interaction in toxicoses or disease states characterized by elevated serum bile salts.