到底是什么原因讓巨噬細(xì)胞積聚在動(dòng)脈斑塊內(nèi),，從而誘發(fā)動(dòng)脈硬化疾?。吭?月8日的《自然-免疫學(xué)》上發(fā)表了一項(xiàng)研究給出了答案,。
研究人員發(fā)現(xiàn),，干擾巨噬細(xì)胞的遷移信號(hào)對(duì)動(dòng)脈硬化的發(fā)生至關(guān)重要，或許能為治療提供線索,。
Kathryn Moore和同事對(duì)患有動(dòng)脈硬化癥的小鼠進(jìn)行研究后發(fā)現(xiàn),，積聚在動(dòng)脈斑塊內(nèi)的巨噬細(xì)胞會(huì)分泌一種名為Netrin-1的分子，而這種分子通常是在人體中起著引導(dǎo)神經(jīng)元遷移的作用,。Netrin-1釋放化學(xué)信號(hào),，使得巨噬細(xì)胞停止遷移并在斑塊內(nèi)積聚。而在通過基因手段去除Netrin-1后,，研究人員發(fā)現(xiàn)動(dòng)脈硬化癥狀得到緩解,，斑塊中積聚的巨噬細(xì)胞數(shù)量也有所減少。(生物谷 Bioon.com)
doi:10.1038/ni.2205
PMC:
PMID:
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.
