Identification of hemopexin as an anti-inflammatory factor that inhibits synergy of hemoglobin with HMGB1 in sterile and infectious inflammation.
Identification of hemopexin as an anti-inflammatory factor that inhibits synergy of hemoglobin with HMGB1 in sterile and infectious inflammation.
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DOI：
10.4049/jimmunol.1103623
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发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Warren HS
中科院分区：
文献类型：
--
作者：
Lin T;Sammy F;Yang H;Thundivalappil S;Hellman J;Tracey KJ;Warren HS
在许多临床环境中，血红蛋白从溶解的红细胞中释放。HMGB1是从损伤细胞释放的核和胞质DNA结合蛋白，已被证明在诱导炎症中起重要作用。由于这两种内源性分子经常存在于坏死和炎症部位，我们研究了它们对巨噬细胞活化的相互作用。我们在这里报告，血红蛋白和HMGB1协同激活小鼠巨噬细胞释放显着增加促炎细胞因子。添加通过TLR2或TLR4激活的微生物配体导致内源性和微生物配体之间的“3向”协同作用的进一步显著增加。这种协同作用被血红素结合素（一种内源性血红素结合血浆蛋白）强烈抑制。研究结果表明，血红蛋白可能在无菌和感染性炎症中起重要作用，内源性血红素结合蛋白可以调节这种反应。在以细胞外血红蛋白和HMGB1升高为特征的临床环境中，使用血液结合素可能是有益的。
Hemoglobin is released from lysed red blood cells in numerous clinical settings. HMGB1 is a nuclear and cytosolic DNA-binding protein released from injured cells that has been shown to play an important role in inducing inflammation. Because both of these endogenous molecules are frequently present in sites of necrosis and inflammation, we studied their interaction on the activation of macrophages. We report here that hemoglobin and HMGB1 synergize to activate mouse macrophages to release significantly increased pro-inflammatory cytokines. Addition of microbial ligands that activate through TLR2 or TLR4 resulted in further significant increases, in a “3-way” synergy between endogenous and microbial ligands. The synergy was strongly suppressed by hemopexin, an endogenous heme-binding plasma protein. The findings suggest that hemoglobin may play an important role in sterile as well as infectious inflammation, and that endogenous hemopexin can modulate this response. Administration of hemopexin may be beneficial in clinical settings characterized by elevated extracellular hemoglobin and HMGB1.
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