Sphingosine-1-phosphate inhibits acid sphingomyelinase and blocks apoptosis in macrophages.

Sphingosine-1-phosphate (Sph-1-P) regulates critical cellular functions including cell proliferation, differentiation, angiogenesis, and cell survival. However, its mechanisms of action are incompletely understood. Here, we show a novel biological effect of Sph-1-P: inhibition of acidic sphingomyelinase (A-SMase) activity in apoptotic bone marrow-derived macrophages. A-SMase catalyzes the conversion of sphingomyelin to ceramides, which are pro-apoptotic. This action of Sph-1-P prevents the accumulation of ceramides and blocks apoptosis, thereby promoting survival of the macrophages.