Ceramide‐independent CD28 and TCR signaling but reduced IL‐2 secretion in T cells of acid sphingomyelinase‐deficient mice
Ceramide‐independent CD28 and TCR signaling but reduced IL‐2 secretion in T cells of acid sphingomyelinase‐deficient mice
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DOI：
10.1002/(sici)1521-4141(199803)28:03
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发表时间：
1998-03
影响因子：
5.4
通讯作者：
B. Stoffel;P. Bauer;Michael G. D. Nix;K. Deres;Wilhelm Stoffel
中科院分区：
文献类型：
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作者：
B. Stoffel;P. Bauer;Michael G. D. Nix;K. Deres;Wilhelm Stoffel
已提出由溶酶体酸性鞘磷脂酶（aSMase）产生的神经酰胺有助于CD 28共刺激信号传导途径。我们使用aSM酶缺陷小鼠系（asmase − / −）来阐明aSM酶在抗CD 3和抗CD 28抗体、凝集素伴刀豆球蛋白A（Con A）或超抗原葡萄球菌肠毒素B联合刺激的脾细胞中的作用。所有刺激物均显示诱导IL-2表达，Con A另外触发高亲和力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CD 3/抗CD 28或Con A刺激的aSMase缺陷型脾细胞的增殖在72小时后降低高达50%。我们得出结论，aSMase产生的神经酰胺不参与CD 28信号转导，而是分泌系统的扰动导致aSMase缺陷型脾细胞增殖受损。
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.