Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.
Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.
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DOI：
10.1126/science.1240342
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发表时间：
2013-08-16
期刊：
影响因子：
--
通讯作者：
Corry DB
中科院分区：
文献类型：
--
作者：
Millien VO;Lu W;Shaw J;Yuan X;Mak G;Roberts L;Song LZ;Knight JM;Creighton CJ;Luong A;Kheradmand F;Corry DB
蛋白酶和先天免疫受体Toll样受体4（TLR4）对于过敏性炎症和疾病（如哮喘）的表达是必需的。连接这些炎症介质的机制对于解释过敏性疾病的基本基础是必不可少的，但一直难以捉摸。在这里，我们证明了TLR4被气道蛋白酶活性激活，启动过敏性气道疾病和抗真菌免疫。这些结果是由凝血蛋白纤维蛋白原的蛋白酶切割诱导的，产生纤维蛋白原切割产物，其充当气道上皮细胞和巨噬细胞上的TLR4配体。因此，过敏性气道炎症代表了由纤维蛋白原裂解和TLR4活化驱动的抗真菌防御策略。这些发现阐明了过敏性疾病的分子基础，并提出了新的治疗策略。
Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies.
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DOI：
10.1016/j.jaci.2010.02.035
发表时间：
2010-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Singh M;Lee SH;Porter P;Xu C;Ohno A;Atmar RL;Greenberg SB;Bandi V;Gern J;Amineva S;Aminev A;Skern T;Smithwick P;Perusich S;Barrow N;Roberts L;Corry DB;Kheradmand F
通讯作者：
Kheradmand F
由 Toll 样受体复合蛋白的功能模拟引起的过敏性。
影响因子：
64.8
作者：
Trompette, Aurelien;Divanovic, Senad;Visintin, Alberto;Blanchard, Carine;Hegde, Rashmi S.;Madan, Rajat;Thorne, Peter S.;Wills-Karp, Marsha;Gioannini, Theresa L.;Weiss, Jerry P.;Karp, Christopher L.
通讯作者：
Karp, Christopher L.
影响因子：
15.9
作者：
Piggott, DA;Eisenbarth, SC;Bottomly, K
通讯作者：
Bottomly, K
DOI：
10.1073/pnas.85.18.6880
发表时间：
1988-09-01
影响因子：
11.1
作者：
PENE, J;ROUSSET, F;DEVRIES, JE
通讯作者：
DEVRIES, JE
影响因子：
4.8
作者：
Okamura, Y;Watari, M;Strauss, JF
通讯作者：
Strauss, JF