Critical role of NK cells rather than Vα14+NKT cells in lipopolysaccharide-induced lethal shock in mice
Critical role of NK cells rather than Vα14+NKT cells in lipopolysaccharide-induced lethal shock in mice
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DOI：
10.4049/jimmunol.169.3.1426
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Kaufmann, SHE
中科院分区：
文献类型：
--
作者：
Emoto, M;Miyamoto, M;Kaufmann, SHE
尽管巨噬细胞在感染性休克的发病机制中发挥着核心作用，但 NK1(+) 细胞也参与其中。 NK1(+)细胞包括两个主要群体，即NK细胞和Valpha14(+)NKT细胞。为了评估这些 NK1(+) 细胞对 LPS 诱导的休克的相对贡献，我们将缺乏 Valpha14(+)NKT 细胞（但不含 NK 细胞）的 β(2)-微球蛋白 (beta(2)m)(-/-) 小鼠与野生型 (WT) 小鼠对 LPS 诱导的休克的易感性进行了比较。结果表明，β(2)m(-/-) 小鼠比 WT 小鼠更容易受到 LPS 诱导的休克的影响。 β(2)m(-/-)小鼠中LPS攻击后的IFN-γ血清水平显着升高，内源性IFN-γ中和或体内NK1(+)细胞的耗竭使β(2)M(-/-)小鼠免受LPS的致命影响。细胞内细胞因子染色显示 NK 细胞是 IFN-γ 的主要产生者。完全缺乏Valpha14(+)NKT细胞的Jalpha281(-/-)小鼠比杂合子同窝小鼠对LPS诱导的休克稍微更敏感。因此，LPS诱导的休克可以在没有Valpha14(+)NKT细胞的情况下被诱导，并且来自NK细胞的IFN-α参与了该机制。在 WT 小鼠中，不同细胞群的等级贡献似乎很可能。
Although macrophages play a central role in the pathogenesis of septic shock, NK1(+) cells have also been implicated. NK1(+) cells comprise two major populations, namely NK cells and Valpha14(+)NKT cells. To assess the relative contributions of these NK1(+) cells to LPS-induced shock, we compared the susceptibility to LPS-induced shock of beta(2)-microglobulin (beta(2)m)(-/-) mice that are devoid of Valpha14(+)NKT cells, but not NK cells, with that of wild-type (WT) mice. The results show that beta(2)m(-/-) mice were more susceptible to LPS-induced shock than WT mice. Serum levels of IFN-gamma following LPS challenge were significantly higher in beta(2)m(-/-) mice, and endogenous IFN-gamma neutralization or in vivo depletion of NK1(+) cells rescued beta(2)M(-/-) mice from lethal effects of LPS. Intracellular cytokine staining revealed that NK cells were major IFN-gamma producers. The Jalpha281(-/-) mice that are exclusively devoid of Valpha14(+)NKT cells were slightly more susceptible to LPS-induced shock than heterozygous littermates. Hence, LPS-induced shock can be induced in the absence of Valpha14(+)NKT cells and IFN-alpha from NK cells is involved in this mechanism. In WT mice, hierarchic contribution of different cell populations appears likely.