Enhanced Membrane Fluidization and Cholesterol Displacement by 1-Heptanol Inhibit Mast Cell Effector Functions

Signal transduction by the high-affinity IgE receptor (FcεRI) depends on membrane lipid and protein compartmentalization. Recently published data show that cells treated with 1-heptanol, a cell fluidizer, exhibit changes in properties. However, functional consequences of 1-heptanol-induced mast signaling are unknown. This study shows short-term exposure to 1-heptanol reduces thermal stability dysregulates at multiple levels. Cells exhibited increased lateral mobility decreased internalization FcεRI. this did not affect initial phosphorylation FcεRI-β chain components SYK/LAT1/PLCγ1 pathway after antigen activation. In contrast, inhibited SAPK/JNK effector functions such as calcium response, degranulation, cytokine production. Membrane hyperfluidization induced heat shock-like response via expression shock 70, diffusion ORAI1-mCherry, unsatisfactory performance STIM1-ORAI1 coupling, determined flow-FRET. Furthermore, antigen-induced production reactive oxygen species potentiated stress-induced plasma permeability interfering 70 activity. The combined suggest 1-heptanol-mediated fluidization does interfere earliest biochemical steps FcεRI signaling, SYK/LAT/PLCγ1 pathway, instead inhibiting functions, including degranulation