The characterization of immune cells in Asm-overexpressed mice

Abstract

Lysosomal enzyme acid sphingomyelinase (ASM) is known for regulating cellular ceramide, by converting sphingomyelin (SM) into ceramide. Mutations in SMPD1, the ASM encoding gene, cause Niemann-Pick disease with the symptoms of progressive hepatosplenomegaly, pulmonary defects, heart and brain disease. The alternation of Asm activity results in abnormal level of ceramide, and is involved in cancer, neuro-degeneration, cardiovascular diseases, apoptosis, and cystic fibrosis. There are a few studies demonstrating the relation of Asm with immune cells, however, its role is yet to be confirmed. The tAsm mouse model is a Smpd1 (sphingomyelin phosphodiesterase 1) transgen-ic mouse line, in which Asm is overexpressed. Using this mouse model the direct re-lation in between Asm and immune system could be studied. Leucocytes are the ma-jor cell type in the immune system. These cells include lymphocytes, monocytes and neutrophils. They develop in the bone marrow and thymus and migrate to different lymphoid organs for their functions once mature. The present study focuses on the characterization of tAsm mice on T lymphocytes, B lymphocytes, and macrophages in the lymphoid organs spleen, lymph node and thymus. The migration, innate and adaptive response were examined. Asm overexpression did not seem to have effect on T lymphocytes, B lymphocytes, and macrophages without immunization, because there was no obvious change in populations and lo-calization. Interestingly, B cells and dendritic cells were seen closely related to ceramide-expressing cells. The current study confirmed that the tAsm mouse model provide a useful platform for immunological researches, since it showed baseline close to the wildtype (WT) healthy mice. Our findings also revealed the potential roles of B cells and dendritic cells in Asm overexpression.