到底是什么原因让巨噬细胞积聚在动脉斑块内，从而诱发动脉硬化疾病？在1月8日的《自然-免疫学》上发表了一项研究给出了答案。
研究人员发现，干扰巨噬细胞的迁移信号对动脉硬化的发生至关重要，或许能为治疗提供线索。
Kathryn Moore和同事对患有动脉硬化症的小鼠进行研究后发现，积聚在动脉斑块内的巨噬细胞会分泌一种名为Netrin-1的分子，而这种分子通常是在人体中起着引导神经元迁移的作用。Netrin-1释放化学信号，使得巨噬细胞停止迁移并在斑块内积聚。而在通过基因手段去除Netrin-1后，研究人员发现动脉硬化症状得到缓解，斑块中积聚的巨噬细胞数量也有所减少。(生物谷 Bioon.com)
doi:10.1038/ni.2205
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The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques
Janine M van Gils, Merran C Derby, Luciana R Fernandes, Bhama Ramkhelawon, Tathagat D Ray, Katey J Rayner, Sajesh Parathath, Emilie Distel, Jessica L Feig, Jacqueline I Alvarez-Leite, Alistair J Rayner, Thomas O McDonald, Kevin D O'Brien, Lynda M Stuart, Edward A Fisher, Adam Lacy-Hulbert & Kathryn J Moore,
Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation.
