Alarmin function of galectin-9 in murine respiratory tularemia.
Alarmin function of galectin-9 in murine respiratory tularemia.
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DOI：
10.1371/journal.pone.0123573
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sharma J
中科院分区：
文献类型：
--
作者：
Steichen AL;Simonson TJ;Salmon SL;Metzger DW;Mishra BB;Sharma J
脓毒症是一种复杂的免疫疾病，其特征在于全身性炎症过度。Alarmins是一种多功能的内源性因子，在包括脓毒症在内的许多免疫性疾病中参与炎症的加重。在这里，我们表明，半乳糖凝集素-9，宿主内源性β-半乳糖苷结合凝集素，作为一种报警蛋白，能够介导脓毒症期间的炎症反应，由肺部感染与新杀弗朗西斯菌，革兰氏阴性细菌病原体。我们的研究结果表明，这种半乳糖凝集素是上调，并可能在肺组织损伤的F。novicida感染败血症小鼠。在体外，纯化的重组galectin-9加重了F。novicida诱导巨噬细胞和中性粒细胞产生炎症介质。同时，半乳糖凝集素-9缺陷（Gal-9-/-）小鼠在其肺中表现出改善的肺病理学、减少的细胞死亡和减少的白细胞浸润，特别是嗜中性粒细胞。这与F. novicida感染的Gal-9-/-小鼠与它们的野生型对应物相比。总的来说，这些研究结果表明，半乳糖凝集素-9作为一种新的报警蛋白的功能，通过增强炎症反应，脓毒症的发展过程中，肺F。杀线虫感染。
Sepsis is a complex immune disorder that is characterized by systemic hyperinflammation. Alarmins, which are multifunctional endogenous factors, have been implicated in exacerbation of inflammation in many immune disorders including sepsis. Here we show that Galectin-9, a host endogenous β-galactoside binding lectin, functions as an alarmin capable of mediating inflammatory response during sepsis resulting from pulmonary infection with Francisella novicida, a Gram negative bacterial pathogen. Our results show that this galectin is upregulated and is likely released during tissue damage in the lungs of F. novicida infected septic mice. In vitro, purified recombinant galectin-9 exacerbated F. novicida-induced production of the inflammatory mediators by macrophages and neutrophils. Concomitantly, Galectin-9 deficient (Gal-9-/-) mice exhibited improved lung pathology, reduced cell death and reduced leukocyte infiltration, particularly neutrophils, in their lungs. This positively correlated with overall improved survival of F. novicida infected Gal-9-/- mice as compared to their wild-type counterparts. Collectively, these findings suggest that galectin-9 functions as a novel alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.
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影响因子：
8.7
作者：
Broz P;Monack DM
通讯作者：
Monack DM
DOI：
10.1186/cc13810
发表时间：
2014-03-31
期刊：
Critical care (London, England)
影响因子：
--
作者：
Fink MP
通讯作者：
Fink MP
影响因子：
3.7
作者：
Mishra BB;Li Q;Steichen AL;Binstock BJ;Metzger DW;Teale JM;Sharma J
通讯作者：
Sharma J
影响因子：
7.3
作者：
Foell, D.;Wittkowski, H.;Clancy, R.
通讯作者：
Clancy, R.
影响因子：
4.4
作者：
Milovanovic, Marija;Volarevic, Vladislav;Lukic, Miodrag L.
通讯作者：
Lukic, Miodrag L.