Background: FAS has been shown to be involved in the regulation of many immune processes by induction of cellular apoptosis. However, accumulated evidence shows that FAS signaling also exhibits nonapoptotic functions, such as induction of cell proliferation and differentiation. FAS is the only death receptor known to be expressed on murine mast cells (MCs).
Objective: To evaluate the role of FAS on murine MC maturation.
Methods: Mouse bone marrow-derived MCs (BMMCs) or peritoneal MCs were derived from FAS-deficient, FASlpr/lpr, and congenic wild-type strains. The MC degranulation and cytokine release after IgE activation was assessed by measuring β-hexosaminidase, interleukin 13, and tumor necrosis factor α release. Transmission electron microscopy analysis was performed to evaluate the level of BMMC maturation. The surface markers and intracellular preformed mediators were measured as well.
Results: Our data reveal that FAS deficiency has an impact on IgE-dependent activation of BMMCs, resulting in a significant decrease in β-hexosaminidase, interleukin 13, and tumor necrosis factor α release. The total content of preformed mediators (eg, tryptase and β-hexosaminidase) was reduced in BMMCs derived from FAS-deficient mice. We also found that the level of FcεRI in peritoneal mast cells from FAS-deficient mice was significantly diminished. FAS deficiency also influenced the kinetics of BMMC maturation as was revealed by transmission electron microscopy analysis.
Conclusion: Our data show that FAS has an impact on the regulation of mouse MC maturation in vitro.
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