Ceramide kinase is not essential but might act as an Ca2+-sensor for mast cell activation

Ceramide kinase (CerK) catalyzes the conversion of ceramide to ceramide 1-phosphate (C1P). We previously revealed that CerK is involved in the activation of mast cells. In this study, we performed an advanced investigation into the role of CerK on the activation of mast cells using CERK−/− mice. Although CERK−/− mice were less prone to exhibiting a passive cutaneous anaphylactic shock (PCA)-reaction compared to wild type (WT) mice, the differences were not significant. In bone marrow-derived mast cells (BMMC) activated by cross-linking antigen (Ag)/IgE, not high, but low concentrations of Ag had a reduced effect on degranulation in BMMC from CERK−/− mice compared to effects on BMMC from WT mice. Similarly, when the BMMCs were activated with calcium ionophore to focus on the downstream signaling of Ca2+-elevation, only a low concentration of ionophore had a reduced effect on degranulation in the BMMC from CERK−/− mice compared to the effect on BMMC from WT mice. Furthermore, the CerK inhibitor K1 reduced the differences in degranulation observed between the BMMC from CERK−/− and WT mice in a dose-dependent manner, demonstrating a contribution for CerK and its product C1P in degranulation. Although CerK is not essential for activation of mast cells, especially a potent and acute activation such as a PCA reaction, CerK might act as an modulator for mild and chronic activation of mast cells, thus increasing sensitivity to cytoplasmic Ca2+.

Research highlights▶ CerK is not essential for potent and acute activation of mast cells. ▶ Not high, but low concentrations of antigen had a reduced effect on degranulation in CERK−/− BMMC. ▶ Not high, but low concentrations of A23187 had a reduced effect on degranulation in CERK−/− BMMC. ▶ The CerK inhibitor K1 reduced the differences in degranulation observed between CERK−/− and WT BMMC in a dose-dependent manner. ▶ CerK might act as a modulator for mild and chronic activation of mast cells.