Publication: The Synergy of Endotoxin and (1→3)-β-D-Glucan, from Gut Translocation, Worsens Sepsis Severity in a Lupus Model of Fc Gamma Receptor IIb-Deficient Mice
Issued Date
2018-06-01
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16628128
1662811X
1662811X
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2-s2.0-85041607504
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Innate Immunity. Vol.10, No.3 (2018), 189-201
Suggested Citation
Jiraphorn Issara-Amphorn, Saowapha Surawut, Navaporn Worasilchai, Arthid Thim-Uam, Malcolm Finkelman, Ariya Chindamporn, Tanapat Palaga, Nattiya Hirankarn, Prapaporn Pisitkun, Asada Leelahavanichkul The Synergy of Endotoxin and (1→3)-β-D-Glucan, from Gut Translocation, Worsens Sepsis Severity in a Lupus Model of Fc Gamma Receptor IIb-Deficient Mice. Journal of Innate Immunity. Vol.10, No.3 (2018), 189-201. doi:10.1159/000486321 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46650
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Title
The Synergy of Endotoxin and (1→3)-β-D-Glucan, from Gut Translocation, Worsens Sepsis Severity in a Lupus Model of Fc Gamma Receptor IIb-Deficient Mice
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Abstract
© 2018 S. Karger AG, Basel. We investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in a lupus model with Fc gamma receptor IIb-deficient (FcGRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. Spontaneous gut leakage, determined by (i) the presence of FITC-dextran, (ii) elevated serum endotoxin, and (iii) elevated serum (1→3)-β-D-glucan (BG), was demonstrated in symptomatic lupus but not in the asymptomatic group. In parallel, spontaneous gut leakage, detected by elevated serum BG without fungal infection, was demonstrated in patients with active lupus nephritis. Gut leakage induced by dextran sulfate solution (DSS) or endotoxin administration together with BG or endotoxin alone, but not BG alone, enhanced the severity of cecal ligation and puncture (CLP) sepsis more prominently in 8-week-old FcGRIIb-/- mice. Additionally, the bone marrow-derived macrophages of FcGRIIb-/- mice produced higher cytokine levels when coexposed to endotoxin and BG, when compared to wild-type mice. In summary, spontaneous gut leakage was demonstrated in symptomatic FcGRIIb-/- mice and the induction of gut permeability worsened sepsis severity. Gut translocation of endotoxin and BG had a minor effect on wild-type mice, but the synergistic effect of BG and endotoxin was prominent in FcGRIIb-/- mice. The data suggest that therapeutic strategies addressing gut leakage may be of interest in sepsis conditions in patients with lupus.