Bile acids induce eosinophil degranulation by two different mechanisms

Abstract

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 mol/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 mol/L TCDCA vigorously produced superoxide and interleukin-8 (IL-8). In contrast, at higher concentrations (e.g., > 1,000 mol/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 mol/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. (HEPATOLOGY 2001;33:582-590.)

MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight

“…Furthermore, BAs inhibit the lipopolysaccharide (LPS)‐induced expression of the proinflammatory cytokines TNF‐α and IL‐6 in primary human macrophages . In contrast, it has been found that treatment of eosinophils with TCDCA and TUDCA induced the production of high amounts of IL‐8 . Thus, the functional influence of BAs on the immune system may vary depending on different immune cell types and conditions.…”

“…A minor fraction of BAs escapes the enterohepatic circulation and reaches the systemic circulation where they regulate many processes, including lipid and glucose homeostasis, intestinal motility, inflammation and configuration and growth of the gut microbiome . A direct impact of BAs on the function of innate immune cells such as monocytes, macrophages and granulocytes has been reported .…”

Dissection of the hierarchy and synergism of the bile derived signal on Cryptosporidium parvum excystation and infectivity

“…Previously we have demonstrated that solar radiation can rapidly induce sporozoite de-granulation, significantly affecting the ability of sporozoites to successfully attach and infect a compatible host cell (King et al 2010). Interestingly, bile salts have previously been demonstrated to induce de-granulation (relating to secretion and exocytosis) in a range of mammalian cells (Hardcastle et al 2001; Yamazaki et al 2001). This work provides the first evidence that bile, and in particular a bile salt, can directly affect intracellular calcium signalling in an Apicomplexan, and to our knowledge provides only the second report of an external host signal associated with affecting intracellular calcium signalling and controlled secretion of apical organelles (Singh et al 2010).…”