کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5833849 | 1122634 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of LPS toxicity by hepatic argininosuccinate synthase (ASS): Novel roles for ASS in innate immune responses to bacterial infection
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Inhibition of LPS toxicity by hepatic argininosuccinate synthase (ASS): Novel roles for ASS in innate immune responses to bacterial infection Inhibition of LPS toxicity by hepatic argininosuccinate synthase (ASS): Novel roles for ASS in innate immune responses to bacterial infection](/preview/png/5833849.png)
چکیده انگلیسی
Lipopolysaccharide (LPS), a structural component of Gram-negative bacteria, is implicated in the pathogenesis of endotoxemia/sepsis and multi-organ injury, including liver damage. We have shown that argininosuccinate synthase (ASS), a hepatic enzyme of the urea cycle, accumulates in circulation within 1 h after treatment with both LPS alone and hepatotoxic combination of LPS and d-Galactosamine. These findings indicate ASS as a sensitive biomarker of liver responses to bacterial endotoxin. Furthermore, we suggest that the ASS release represents a potential counteracting liver reaction to LPS, and demonstrates anti-LPS activity of recombinant ASS (rASS) in vitro and in rodent models of endotoxemia in vivo. rASS physically bound to LPS, as indicated by a gel shift assay, and suppressed Escherichia coli growth in cultures consistent with direct antimicrobial properties of ASS. rASS reduced LPS cytotoxicity, TNF-α production, and increased cell viability in cultured mouse macrophages, even when added one hour following LPS challenge. Intraperitoneal injection of rASS (5 mg/kg) after treatment with a high dose of LPS remarkably increased survival of rodents, with a concomitant decrease of sepsis markers TNF-α, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels in blood. These results suggest that the endogenous ASS constitutes a novel liver-derived component of the innate immune response to bacterial LPS, and that recombinant ASS could mitigate the lethal effects of bacterial endotoxins during sepsis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 11, Issue 9, September 2011, Pages 1180-1188
Journal: International Immunopharmacology - Volume 11, Issue 9, September 2011, Pages 1180-1188
نویسندگان
Victor Prima, Alvin Wang, Gabriel Molina, Kevin K.W. Wang, Stanislav I. Svetlov,