TY  - JOUR
A1  - Jbeily, Nayla
A1  - Suckert, Iris
A1  - Gonnert, Falk A.
A1  - Acht, Benedikt
A1  - Bockmeyer, Clemens L.
A1  - Grossmann, Sascha D.
A1  - Blaess, Markus F.
A1  - Lüth, Anja
A1  - Deigner, Hans-Peter
A1  - Bauer, Michael
A1  - Claus, Ralf A.
T1  - Hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response
JF  - Journal of lipid research
N2  - Plasma secretion of acid sphingomyelinase is a hallmark of cellular stress response resulting in the formation of membrane embedded ceramide-enriched lipid rafts and the reorganization of receptor complexes. Consistently, decompartmentalization of ceramide formation from inert sphingomyelin has been associated with signaling events and regulation of the cellular phenotype. Herein, we addressed the question of whether the secretion of acid sphingomyelinase is involved in host response during sepsis. We found an exaggerated clinical course in mice genetically deficient in acid sphingomyelinase characterized by an increased bacterial burden, an increased phagocytotic activity, and a more pronounced cytokine storm. Moreover, on a functional level, leukocyte-endothelial interaction was found diminished in sphingomyelinase-deficient animals corresponding to a distinct leukocytes' phenotype with respect to rolling and sticking as well as expression of cellular surface proteins.(jlr) We conclude that hydrolysis of membrane-embedded sphingomyelin, triggered by circulating sphingomyelinase, plays a pivotal role in the first line of defense against invading microorganisms. This function might be essential during the early phase of infection leading to an adaptive response of remote cells and tissues.-Jbeily, N., I. Suckert, F. A. Gonnert, B. Acht, C. L. Bockmeyer, S. D. Grossmann, M. F. Blaess, A. Lueth, H.-P. Deigner, M. Bauer, and R. A. Claus. Hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response. J. Lipid Res. 2013. 54: 410-424.
KW  - sphingomyelin phosphodiesterase 1
KW  - inflammation
KW  - sepsis
KW  - gene expression
KW  - survival
KW  - leukocyte-endothelial interaction
KW  - trans-migration
KW  - organ failure
Y1  - 2013
U6  - https://doi.org/10.1194/jlr.M031625
SN  - 0022-2275
VL  - 54
IS  - 2
SP  - 410
EP  - 424
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Lang, Judith
A1  - Bohn, Patrick
A1  - Bhat, Hilal
A1  - Jastrow, Holger
A1  - Walkenfort, Bernd
A1  - Cansiz, Feyza
A1  - Fink, Julian
A1  - Bauer, Michael
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Lang, Karl S.
T1  - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
JF  - Nature Communications
N2  - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
KW  - immunology
KW  - infection
KW  - membrane fusion
KW  - phagocytosis
KW  - sphingolipids
Y1  - 2020
U6  - https://doi.org/10.1038/s41467-020-15072-8
SN  - 2041-1723
VL  - 11
IS  - 1
SP  - 1
EP  - 15
PB  - Nature Publishing Group UK
CY  - London
ER  -