Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice

European Journal of Immunology
B StoffelW Stoffel

Abstract

Ceramide generated by lysosomal acid sphingomyelinase (aSMase) has been proposed to contribute to CD28 co-stimulatory signaling pathways. We used an aSMase-deficient mouse line (asmase-/-) to elucidate the role of the aSMase in splenocytes stimulated with either a combination of anti-CD3 and anti-CD28 antibodies, the lectin concanavalin A (Con A) or the superantigen staphylococcal enterotoxin B. All stimuli were shown to induce IL-2 expression, Con A additionally triggered the expression of high-affinity IL-2 receptor. However, in asmase-/- mice secretion of IL-2 was significantly reduced, whereas the intracellular IL-2 levels were elevated. Proliferation of anti-CD3/anti-CD28 or Con A-stimulated aSMase-deficient splenocytes was reduced up to 50% after 72 h in comparison to wild-type cells. We conclude that ceramide generated by aSMase is not involved in CD28 signal transduction, but rather a perturbation of the secretory system is responsible for the impaired proliferation of aSMase-deficient splenocytes.

References

Jun 1, 1992·Current Opinion in Immunology·Y Liu, P S Linsley
Jan 1, 1992·The Journal of Experimental Medicine·E E Eynon, D C Parker
Jun 30, 1989·Cell·R H Schwartz
Jan 1, 1989·Cold Spring Harbor Symposia on Quantitative Biology·C A JanewayD B Murphy
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D B LewisC B Wilson
Jan 1, 1983·Annual Review of Immunology·K J LaffertyH S Warren
Mar 1, 1994·The Journal of Experimental Medicine·K E TruittJ B Imboden
Jul 1, 1994·Immunology Today·C H JuneC B Thompson
Jul 1, 1995·European Journal of Immunology·G Chan, A Ochi
Jun 1, 1995·The Journal of Experimental Medicine·L M BoucherM Krönke
Jun 1, 1994·Current Opinion in Immunology·A L DeFranco
Jun 1, 1994·Current Opinion in Immunology·B M Sefton, J A Taddie
Aug 1, 1994·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R Kapeller, L C Cantley
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·P A NegulescuM D Cahalan
Jan 1, 1993·Journal of Leukocyte Biology·P V Nash, A M Mastro
May 15, 1997·The Biochemical Journal·D J Sillence, D Allan

❮ Previous
Next ❯

Citations

Sep 23, 2000·Chemistry and Physics of Lipids·T LevadeR Salvayre
Mar 5, 2003·Annual Review of Immunology·Michelle DykstraSusan K Pierce
Feb 7, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C BezombesT Levade
Sep 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Denise TischnerHolger M Reichardt
Jan 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·V P PatelM C Miceli
Jan 8, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·B SéguiT Levade
Dec 19, 2014·PLoS Pathogens·Nora MuellerSibylle Schneider-Schaulies
Mar 18, 2015·Biological Chemistry·Niklas Beyersdorf, Nora Müller
Aug 29, 2019·Frontiers in Cell and Developmental Biology·Elita AvotaSibylle Schneider-Schaulies
May 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hongjiao XiangTao Wu
Apr 27, 1999·Biochimica Et Biophysica Acta·T Levade, J P Jaffrézou
Aug 12, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mohammad TaheriSoudeh Ghafouri-Fard
Jan 31, 2009·The American Journal of Pathology·Peng QuCong Yan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.