Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice
Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice
复制标题
抗 Semaphorin 3A 中和单克隆抗体可预防脂多糖治疗小鼠败血症的发生
DOI：
10.1093/intimm/dxv014
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发表时间：
2015
影响因子：
4.4
通讯作者：
Koji Murakami and Yoshio Goshima
中科院分区：
文献类型：
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作者：
Naoya Yamashita;Aoi Jitsuki-Takahashi;Miyuki Ogawara;Wataru Ohkubo;Tomomi Araki;Chie Hotta;Tomohiko Tamura;Shu-ichi Hashimoto;Takashi Yabuki;Toru Tsuji;Yukie Sasakura;Hiromi Okumura;Aki Takaiwa;Chika Koyama;Koji Murakami and Yoshio Goshima
Semaphorin 3A (Sema3A) 最初被认为是感觉神经元发育过程中的有效生长锥塌陷因子，现在被认为是免疫、心血管、骨代谢和神经系统中的关键参与者。在这里，我们建立了一种抗 Sema3A 单克隆抗体，可以在体外和体内中和 Sema3A 的作用。通过结合自主多样化文库选择系统和体外生长锥塌陷测定来筛选抗Sema3A中和鸡IgM抗体。我们进一步开发了功能阻断性鸡鼠嵌合和人源化抗 Sema3A 抗体。我们发现我们的抗 Sema3A 抗体可有效提高脂多糖诱导的败血症小鼠的存活率。我们的抗体是一种潜在的治疗剂，可以预防与 Sema3A 相关的人类疾病的发作或减轻其症状。
Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A bothin vitroandin vivo. The anti-Sema3A neutralization chick IgM antibodies were screened by combining an autonomously diversifying library selection system and anin vitrogrowth cone collapse assay. We further developed function-blocking chick-mouse chimeric and humanized anti-Sema3A antibodies. We found that our anti-Sema3A antibodies were effective for improving the survival rate in lipopolysaccharide-induced sepsis in mice. Our antibody is a potential therapeutic agent that may prevent the onset of or alleviate symptoms of human diseases associated with Sema3A.