A rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease.
A rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease.
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感染性肺部疾病中巨噬细胞衍生的多功能蛋白聚糖和透明质酸快速增加。
DOI：
10.1016/j.matbio.2014.01.011
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发表时间：
2014-02
期刊：
影响因子：
6.9
通讯作者：
Frevert, Charles W.
中科院分区：
文献类型：
--
作者：
Chang, Mary Y.;Tanino, Yoshinori;Vidova, Veronika;Kinsella, Michael G.;Chan, Christina K.;Johnson, Pamela Y.;Wight, Thomas N.;Frevert, Charles W.
这项研究的目的是描述革兰氏阴性细菌感染急性反应中肺内硫酸软骨素蛋白多糖和透明质酸的变化，并确定导致这些变化的细胞成分。小鼠经气管内注射活菌(IT)、大肠杆菌脂多糖(LPS)或PBS。大肠埃希菌和脂多糖均可选择性地引起肺组织VERSICAN和透明质酸合成酶(HAS)亚型1和2mRNA表达的选择性增加，并伴随着VERSICAN和HAS免疫组织化学染色的增强。凡西嘉与肺泡巨噬细胞的一个亚群有关。为了验证巨噬细胞是否有助于多发性硬化和透明质酸的蓄积，我们进行了骨髓和肺泡巨噬细胞原代培养的体外研究。未受刺激的巨噬细胞表达极低水平的杂蛋白和透明质酸合成酶mRNA，没有检测到杂蛋白或透明质酸产物。内毒素刺激后，细胞内VERSICA基因和蛋白的表达迅速增加，Has1基因的表达迅速增加，透明质酸降解酶1和2的降解受到抑制。氯喹处理后可检测到透明质酸，表明巨噬细胞迅速周转和降解透明质酸。此外，还比较了M1巨噬细胞经典激活激动剂内毒素与M2a和M2c交替激活激动剂IL-4/IL-13或IL-10的作用。Verscan和Has1只有在M1激活时才会增加。最后，在TLR4−/−小鼠中，野生型小鼠全肺中VERSICAN和HAS1的表达上调被完全取消。这些发现表明，凡西嘉和透明质酸的合成可能在革兰氏阴性肺部感染的先天免疫反应中发挥重要作用。
The goals of this study were to characterize the changes to chondroitin sulfate proteoglycans and hyaluronan in lungs in the acute response to gram-negative bacterial infection, and to identify cellular components responsible for these changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1 and 2 associated with increased immunohistochemical and histochemical staining for versican and hyaluronan in the lungs. Versican was associated with a subset of alveolar macrophages. To examine whether macrophages contribute to versican and hyaluronan accumulation, in vitro studies with primary cultures of bone marrow-derived and alveolar macrophages were performed. Unstimulated macrophages expressed very low levels of versican and hyaluronan synthase mRNA, with no detectible versican protein or hyaluronan product. Stimulation with LPS caused rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading enzymes. Hyaluronan could be detected following chloroquine pre-treatment, indicating rapid turnover and degradation of hyaluronan by macrophages. In addition, the effects of LPS, the M1 macrophage classical activation agonist, were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative activation agonists, respectively. Versican and Has1 increased only in response to M1 activation. Finally, the up-regulation of versican and Has1 in the whole lungs of wild-type mice following IT LPS was completely abrogated in TLR-4−/− mice. These findings suggest that versican and hyaluronan synthesis may play an important role in the innate immune response to gram-negative lung infection.
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DOI：
10.1084/jem.183.3.1119
发表时间：
1996-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
DeGrendele HC;Estess P;Picker LJ;Siegelman MH
通讯作者：
Siegelman MH
影响因子：
6.7
作者：
Hajjar AM;Ernst RK;Fortuno ES 3rd;Brasfield AS;Yam CS;Newlon LA;Kollmann TR;Miller SI;Wilson CB
通讯作者：
Wilson CB
影响因子：
3.3
作者：
BERG, JT;LEE, ST;TSAN, MF
通讯作者：
TSAN, MF
影响因子：
15.9
作者：
Esko, JD;Lindahl, U
通讯作者：
Lindahl, U
影响因子：
9.7
作者：
Franz, Sandra;Allenstein, Francie;Simon, Jan C.
通讯作者：
Simon, Jan C.