Enhancement of FcεRI-mediated degranulation response in the rat basophilic leukemia cell line RBL2H3 by the fluorosurfactants perfluorooctanoic acid and perfluorooctane sulfonate

摘要

The effect of two fluorosurfactants, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), on degranulation of rat basophilic leukemia RBL2H3 cells was investigated. PFOA and PFOS promoted IgE-mediated release of granule components of RBL2H3 cells at 10-300 μM. At low concentrations (<30 μM), the fluorosurfactants failed to induce degranulation, but promoted IgE-mediated degranulation without affecting cell viability. The absence of extracellular Ca~(2+) removed the promoting effect of the fluorosurfactants on IgE-mediated degranulation. On the other hand, the fluorosurfactants at high concentrations (>100 μM) induced release of granule components without IgE-mediated activation in parallel with cell death. Pretreatment of tetradecanoyl-phorbol-acetate, a protein kinase C activator, inhibited both the promoting effect of the fluorosurfactants at low concentration on IgE-mediated degranulation and cell death-associated granule component release by high concentration of the fluorosurfactants. These findings indicate that PFOA and PFOS affect granule component release of mast cells by two different mechanisms, namely enhancement of active degranulation machinery at low concentrations and cell lysis at high concentrations.