Time to Develop Therapeutic Antibodies Against Harmless Proteins Colluding with Sepsis Mediators?
Time to Develop Therapeutic Antibodies Against Harmless Proteins Colluding with Sepsis Mediators?
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DOI：
10.2147/itt.s262605
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发表时间：
2020
影响因子：
7.2
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Li J;Bao G;Wang H
脓毒症是指由微生物感染引起的全身性炎症反应综合征，部分原因是炎症失调和相关的免疫抑制。一种无处不在的核蛋白HMGB1，在败血症的早期阶段由活化的白细胞分泌，以协调炎症反应。当HMGB1被损伤的体细胞大量释放时，可诱导巨噬细胞焦亡和免疫抑制，从而损害宿主根除微生物感染的能力。许多内源性蛋白已被证明与HMGB1结合以调节其细胞外功能。在这里，我们讨论了一种新出现的可能性，即开发针对无害蛋白的治疗性抗体，这些蛋白与致病介质串通，用于人类败血症和其他炎症性疾病的临床管理。
Sepsis refers to a systemic inflammatory response syndrome resulting from microbial infections, and is partly attributable to dysregulated inflammation and associated immunosuppression. A ubiquitous nuclear protein, HMGB1, is secreted by activated leukocytes to orchestrate inflammatory responses during early stages of sepsis. When it is released by injured somatic cells at overwhelmingly higher quantities, HMGB1 may induce macrophage pyroptosis and immunosuppression, thereby impairing the host’s ability to eradicate microbial infections. A number of endogenous proteins have been shown to bind HMGB1 to modulate its extracellular functions. Here, we discuss an emerging possibility to develop therapeutic antibodies against harmless proteins that collude with pathogenic mediators for the clinical management of human sepsis and other inflammatory diseases.