Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene

Scott L. Schissel, Edward H. Schuchman, Kevin Jon Williams, Ira Tabas

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Mammalian sphingomyelinases have been implicated in many important physiological and pathophysiological processes. Although several mammalian sphingomyelinases have been identified and studied, one of these, an acidic Zn2+-stimulated sphingomyelinase (Zn-SMase) originally found in fetal bovine serum, has received little attention since its first and only report 7 years ago. We now show that Zn-SMase activity is secreted by human and murine macrophages, human skin fibroblasts, microglial cells, and several other cells in culture and is markedly up-regulated during differentiation of human monocytes to macrophages. Remarkably, peritoneal macrophages from mice in which the acid SMase gene had been disrupted by homologous recombination secreted no Zn-SMase activity, indicating that this enzyme and the intracellular lysosomal SMase, which is Zn-independent, arise from the same gene. Furthermore, skin fibroblasts from patients with types A and B Niemann- Pick disease, which are known to lack lysosomal SMase activity, also lack Zn- SMase activity in their conditioned media. Chinese hamster ovary cells stably transfected with a cDNA encoding lysosomal SMase massively over-express both cellular lysosomal SMase and secreted Zn-SMase activities. Thus, Zn-SMase arises independently of alternative splicing, suggesting a post- translational process. In summary, a wide variety of cell types secrete Zn- SMase activity, which arises from the same gene as lysosomal SMase. This secreted enzyme may play roles in physiological and pathophysiological processes involving extracellular sphingomyelin hydrolysis.

Original languageEnglish
Pages (from-to)18431-18436
Number of pages6
JournalJournal of Biological Chemistry
Issue number31
StatePublished - 1996


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