Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.
Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.
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DOI：
10.1111/imr.13141
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发表时间：
2023-01
影响因子：
8.7
通讯作者：
中科院分区：
文献类型：
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本综述旨在捕捉动物模型围绕替代途径和放大环 (AP/AL) 在疾病中的作用提供的关键发现。动物模型，特别是小鼠模型，对于定义补体的作用以及健康和疾病中的替代途径非常有用；例如，眼镜蛇毒因子的使用和 C3 的消耗提供了初步认识，即补体对于产生适当的适应性免疫反应至关重要。基因敲除小鼠的发展进一步强调了 AP/AL 在疾病中的重要性，FH 基因敲除小鼠为第一种抗补体药物铺平了道路。 FB、备解素和 C3 敲除小鼠发育的影响与疾病机制的理解密切相关。事实上，我们目前对补体在大多数情况下在某种水平上发挥作用的理解植根于许多体内研究。我们认为，无论有或没有其他公认的 AP 成分，C3 在先天性和适应性免疫、正常生理学和细胞功能中的作用都超出了显而易见的范围，只会扩展补体系统这一臂的范围。人源化小鼠模型也继续发挥作用。在这里，我们认为过去几十年开发的动物模型确实有助于确定 AP/AL 在疾病中的作用。
This review aimed to capture the key findings that animal models have provided around the role of the alternative pathway and amplification loop (AP/AL) in disease. Animal models, particularly mouse models, have been incredibly useful to define the role of complement and the alternative pathway in health and disease; for instance, the use of cobra venom factor and depletion of C3 provided the initial insight that complement was essential to generate an appropriate adaptive immune response. The development of knockout mice have further underlined the importance of the AP/AL in disease, with the FH knockout mouse paving the way for the first anti‐complement drugs. The impact from the development of FB, properdin, and C3 knockout mice closely follows this in terms of mechanistic understanding in disease. Indeed, our current understanding that complement plays a role in most conditions at one level or another is rooted in many of these in vivo studies. That C3, in particular, has roles beyond the obvious in innate and adaptive immunity, normal physiology, and cellular functions, with or without other recognized AP components, we would argue, only extends the reach of this arm of the complement system. Humanized mouse models also continue to play their part. Here, we argue that the animal models developed over the last few decades have truly helped define the role of the AP/AL in disease.
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影响因子：
4.6
作者：
Choi YJ;Kim JE;Lee SJ;Gong JE;Jin YJ;Lee H;Hwang DY
通讯作者：
Hwang DY
DOI：
10.4049/jimmunol.0901826
发表时间：
2009-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banda NK;Levitt B;Glogowska MJ;Thurman JM;Takahashi K;Stahl GL;Tomlinson S;Arend WP;Holers VM
通讯作者：
Holers VM
影响因子：
3
作者：
Annamalai B;Parsons N;Belhaj M;Brandon C;Potts J;Rohrer B
通讯作者：
Rohrer B
影响因子：
3.7
作者：
Chen H;Liu B;Lukas TJ;Neufeld AH
通讯作者：
Neufeld AH
影响因子：
3.6
作者：
Andrä, J;Halter, R;Paul, D
通讯作者：
Paul, D