Secretory leukocyte protease inhibitor interferes with uptake of lipopolysaccharide by macrophages
Secretory leukocyte protease inhibitor interferes with uptake of lipopolysaccharide by macrophages
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DOI：
10.1128/iai.67.9.4485-4489.1999
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发表时间：
1999-09-01
影响因子：
3.1
通讯作者：
Wright, S
中科院分区：
文献类型：
--
作者：
Ding, A;Thieblemont, N;Wright, S
巨噬细胞是细菌内毒素（LPS）最敏感的靶标之一，通过释放一系列炎症介质对微量LPS作出反应。用分泌性白细胞蛋白酶抑制剂（SLPI）转染巨噬细胞使这些细胞对LPS刺激不敏感。在这里，我们表明，从可溶性CD 14（sCD 14）-LPS复合物的SLPI过表达细胞的LPS摄取只有50%的对照细胞中看到的。SLPI转染子和模拟转染子在表面表达CD 14或CD 18方面没有差异。此外，我们还表明，重组人SLPI可以在体外与纯化的内毒素结合，通过标记LPS的荧光猝灭和非变性聚丙烯酰胺凝胶电泳评估，SLPI引起LPS与sCD 14的结合减少，这些结果表明，SLPI对巨噬细胞对LPS反应的抑制作用可能部分是由于其阻断LPS向可溶性CD 14的转移以及其干扰巨噬细胞从LPS-sCD 14复合物中摄取LPS。
Macrophages are among the most sensitive targets of bacterial endotoxin (LPS), responding to minute amounts of LPS by releasing a battery of inflammatory mediators. Transfection of macrophages with secretory leukocyte protease inhibitor (SLPI) renders these cells refractory to LPS stimulation. Here we show that uptake of LPS from soluble CD14 (sCD14)-LPS complexes by SLPI-overexpressing cells was only 50% of that seen in control cells. SLPI transfectants and mock transfectants did not differ in the surface expression of CD14 or CD18, We show, in addition, that recombinant human SLPI can bind to purified endotoxin in vitro, SLPI caused a decrease in the binding of LPS to sCD14 as assessed both by fluorescence quenching of labeled LPS and by nondenaturing polyacrylamide gel electrophoresis, These results suggest that the inhibitory effect of SLPI on macrophage responses to LPS may, in part, be due to its blockade of LPS transfer to soluble CD14 and its interference with uptake of LPS from LPS-sCD14 complexes by macrophages.