Stoffel B, Bauer P, Nix M, Deres K, Stoffel W
Institute of Medical Microbiology and Hygiene, University of Cologne, Germany.
Eur J Immunol. 1998 Mar;28(3):874-80. doi: 10.1002/(SICI)1521-4141(199803)28:03<874::AID-IMMU874>3.0.CO;2-T.
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.
溶酶体酸性鞘磷脂酶（aSMase）产生的神经酰胺被认为参与了CD28共刺激信号通路。我们使用aSMase缺陷小鼠品系（asmase-/-）来阐明aSMase在用抗CD3和抗CD28抗体组合、凝集素伴刀豆球蛋白A（Con A）或超抗原葡萄球菌肠毒素B刺激的脾细胞中的作用。所有刺激均显示可诱导白细胞介素-2（IL-2）表达，Con A还额外触发了高亲和力IL-2受体的表达。然而，在asmase-/-小鼠中，IL-2的分泌显著减少，而细胞内IL-2水平升高。与野生型细胞相比，抗CD3/抗CD28或Con A刺激的aSMase缺陷脾细胞在72小时后的增殖减少了50%。我们得出结论，aSMase产生的神经酰胺不参与CD28信号转导，而是分泌系统的紊乱导致了aSMase缺陷脾细胞增殖受损。
