title: Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene.
abstract: 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 overexpress 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.
authors.affiliation: Department of Anatomy, Columbia University, New York, New York 10032, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Schissel
authors.forename: E H
authors.initials: EH
authors.lastname: Schuchman
authors.forename: K J
authors.initials: KJ
authors.lastname: Williams
authors.forename: I
authors.initials: I
authors.lastname: Tabas
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009542:Niemann-Pick Diseases / Q000201:enzymology / Q000235:genetics; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D015032:Zinc / Q000494:pharmacology
chemical_list: D013108:Sphingomyelin Phosphodiesterase; D015032:Zinc