研究人员发现，小鼠血管巨噬细胞表达嗅觉受体Olfr2和所有相关的运输和信号分子。Olfr2能检测到化合物辛醛，辛醛能激活NLRP3（NLR family pyrin domain containing 3）炎症小体，并诱导人类和小鼠巨噬细胞分泌白细胞介素-1β。研究人员发现，人类和小鼠血浆中含有辛醛，这是一种脂质过氧化的产物，其浓度足以激活Olfr2和人类嗅觉受体6A2（OR6A2）。提高辛醛水平会加剧动脉粥样硬化，而在小鼠中以Olfr2为基因靶点则会显著减少动脉粥样硬化斑块。这些研究结果表明，抑制OR6A2可能为预防和治疗动脉粥样硬化提供一个有希望的策略。
据介绍，动脉粥样硬化是一种动脉壁的炎症性疾病，涉及巨噬细胞等免疫细胞。嗅觉受体是G蛋白偶联的化学感受器，在探测气味剂和嗅觉方面具有核心作用。
附：英文原文
Title: Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production
Author: Marco Orecchioni, Kouji Kobiyama, Holger Winkels, Yanal Ghosheh, Sara McArdle, Zbigniew Mikulski, William B. Kiosses, Zhichao Fan, Lai Wen, Yunmin Jung, Payel Roy, Amal J. Ali, Yukiko Miyamoto, Matthew Mangan, Jeffrey Makings, Zhihao Wang, Angela Denn, Jenifer Vallejo, Michaela Owens, Christopher P. Durant, Simon Braumann, Navid Mader, Lin Li, Hiroaki Matsunami, Lars Eckmann, Eicke Latz, Zeneng Wang, Stanley L. Hazen, Klaus Ley
Issue&Volume: 2022-01-14
Abstract: Atherosclerosis is an inflammatory disease of the artery walls and involves immune cells such as macrophages. Olfactory receptors (OLFRs) are G protein–coupled chemoreceptors that have a central role in detecting odorants and the sense of smell. We found that mouse vascular macrophages express the olfactory receptor Olfr2 and all associated trafficking and signaling molecules. Olfr2 detects the compound octanal, which activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome and induces interleukin-1β secretion in human and mouse macrophages. We found that human and mouse blood plasma contains octanal, a product of lipid peroxidation, at concentrations sufficient to activate Olfr2 and the human ortholog olfactory receptor 6A2 (OR6A2). Boosting octanal levels exacerbated atherosclerosis, whereas genetic targeting of Olfr2 in mice significantly reduced atherosclerotic plaques. Our findings suggest that inhibiting OR6A2 may provide a promising strategy to prevent and treat atherosclerosis.
DOI: abg3067
Source: https://www.science.org/doi/10.1126/science.abg3067