Fusogenicity of membranes: the impact of acid sphingomyelinase on innate immune responses.
Acid sphingomyelinase (ASMase) has been implemented in cellular signaling mainly because its reaction product, ceramide, has been assumed to be a mediator within signaling pathways. Our studies of three independent infection systems show that ASMase is required for phago-lysosomal fusion in macrophages infected with Listeria monocytogenes, for exocytosis of secretory lysosomes by lymphocytic choriomeningitis virus-specific cytotoxic T cells, and for generation of multinucleated giant cells in granuloma of mice infected with Mycobacterium avium. Because of its neutral lipid nature, ceramide is confined to the membranes of phagosomes and lysosomes or the extracellular leaflet of the plasma membrane. In light of the biochemical and biophysical properties of ceramide, we provide a model suggesting that ASMase regulates select vesicular fusion processes by modifying the steric conformation of cellular membranes.
Utermöhlen
Olaf
O
Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Goldenfelsstrasse 19-21, 50935 Cologne, Germany. olaf.utermoehlen@uk-koeln.de
Herz
Jasmin
J
Schramm
Michael
M
Krönke
Martin
M
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015726:Giant Cells / Q000378:metabolism; D006099:Granuloma / Q000378:metabolism; D007113:Immunity, Innate; D008089:Listeria monocytogenes / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009162:Mycobacterium avium / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism / Q000494:pharmacology*
C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase