Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice.

Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice.
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分泌白细胞抑制剂(SLPI)缺陷小鼠对LPS诱导的内毒素休克的敏感性增加。

DOI:
10.1084/jem.20021824
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发表时间:
2003-03-03
影响因子:
15.3
通讯作者:
Nukiwa, T
Nukiwa, T
中科院分区:
医学1区
文献类型:
--
作者:
Nakamura, A;Mori, Y;Hagiwara, K;Suzuki, T;Sakakibara, T;Kikuchi, T;Igarashi, T;Ebina, M;Miyazaki, J;Takai, T;Nukiwa, T;Nukiwa, T

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分泌性白细胞蛋白酶抑制剂(SLPI)保护组织免受中性粒细胞弹性酶在炎症部位的破坏作用。最近对SLPI新功能的研究表明,SLPI可能在先天免疫中发挥更大的作用,而不仅仅是作为蛋白酶抑制剂。为了阐明SLPI在细菌感染中的功能,我们制造了SLPI缺陷小鼠(SLPI - / -小鼠),并分析了它们对脂多糖(LPS)诱导的实验性内毒素休克的反应。SLPI - / -小鼠内毒素休克死亡率高于野生型小鼠。这可以部分解释为我们观察到SLPI−/−巨噬细胞在LPS处理后比SLPI+/+巨噬细胞表现出更高的白细胞介素6和高迁移率组(HMG)-1的产生和核因子κB活性。SLPI也影响B细胞功能。与SLPI+/+ B细胞相比,LPS处理后的SLPI−/−B细胞的增殖和IgM的产生更多。我们的研究结果表明,SLPI可以减轻过度的炎症反应,从而确保先天免疫的平衡功能。
Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI−/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI−/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI−/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI+/+ macrophages. SLPI also affects B cell function. SLPI−/− B cells show more proliferation and IgM production after LPS treatment than SLPI+/+ B cells. Our results suggest that SLPI attenuates excessive inflammatory responses and thus assures balanced functioning of innate immunity.
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