TY -的T1 CCR2 / CCR5-mediated macrophage-smooth肌细胞在肺动脉高压摩根富林明相声——欧洲呼吸杂志》乔和J - 10.1183/13993003.02308 -2018欧元六世- 54 - 4 SP - 1802308 AU -阿比德,部门非盟-马科斯,伊丽莎白盟——Parpaleix Aurelien AU - Amsellem,瓦莱丽盟——Breau Marielle盟——HoussainiAmal AU - Vienney, Nora AU - Lefevre, Marine AU - Derumeaux, Genevieve AU - Evans, Steven AU - Hubeau, Cedric AU - Delcroix, Marion AU - Quarck, Rozenn AU - Adnot, Serge AU - Lipskaia，N2 -巨噬细胞是肺动脉高压(PAH)发病机制的主要参与者。为了研究肺巨噬细胞和肺动脉平滑肌细胞(PASMCs)是否协同刺激PASMC生长，以及CCL2-CCR2和CCL5-CCR5通路是否抑制巨噬细胞- PASMC相互作用和PAH的发展，我们使用了来自PAH患者和对照组的人类ccr5敲入小鼠和PASMCs。小鼠M1或M2巨噬细胞条件培养液刺激了PASMC的生长。这种效应在M2 -巨噬细胞/PASMC共培养条件培养基中被显著放大。CCR2、CCR5、CCL2和CCL5在巨噬细胞/PASMC共培养中表达上调。与抑制任何一种受体相比，双重CCR2和CCR5抑制更能减弱m2 -巨噬细胞/PASMC共培养条件培养基的促生长作用。在巨噬细胞或PASMCs中删除CCR2或CCR5会减弱生长反应。在缺氧或SUGEN/缺氧诱导的PH小鼠中，针对CCR2和CCR5的PH抑制或逆转比单独针对任何一种受体更有效。与对照组相比，PAH患者PASMCs和血管周围巨噬细胞中CCR2和CCR5表达上调。 The PASMC growth-promoting effect of conditioned media from M2-macrophage/PASMC co-cultures was greater when PASMCs from PAH patients were used in the co-cultures or as the target cells and was dependent on CCR2 and CCR5. PASMC migration toward M2-macrophages was greater with PASMCs from PAH patients and was attenuated by blocking CCR2 and CCR5.CCR2 and CCR5 are required for collaboration between macrophages and PASMCs to initiate and amplify PASMC migration and proliferation during PAH development. Dual targeting of CCR2 and CCR5 may hold promise for treating human PAH.CCR2 and CCR5 are required for collaboration between macrophages and pulmonary artery smooth muscle cells (PASMCs) to initiate and amplify PASMC proliferation. Dual targeting of CCR2 and CCR5 may hold promise for treating pulmonary artery hypertension. http://bit.ly/2L3izU6 ER -