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)/IgL 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 Cl P 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+ (C) 2010 Elsevier Inc All rights reserved