Emergency myelopoiesis contributes to immune cell exhaustion and pulmonary vascular remodelling.
Emergency myelopoiesis contributes to immune cell exhaustion and pulmonary vascular remodelling.
复制标题
DOI：
10.1111/bph.14945
复制
发表时间：
2021-01
影响因子：
7.3
通讯作者：
Bryant AJ
中科院分区：
文献类型：
--
作者：
Fu C;Lu Y;Williams MA;Brantly ML;Ventetuolo CE;Morel LM;Mehrad B;Scott EW;Bryant AJ
继发于慢性肺病的肺动脉高压（PH）（世界卫生组织第3组PH）是致命的，肺移植是唯一可用的长期治疗选择。已知髓源性细胞会影响肺纤维化和PH的进展，但作用机制尚不清楚。因此，我们研究了紧急骨髓生成诱导的骨髓细胞增殖对PH发展的影响以及针对骨髓细胞表达的程序性死亡配体1（PD-L1）的治疗，以预防肺血管重塑。将LysM. Cre-DTR（“mDTR”）小鼠用博来霉素（0.018U·g-1，i. p.）在接受媒介物或白喉毒素（DT; 100 ng，i. p.）在博来霉素方案开始后约4周，进行右心室压力测量并收集组织样品用于组织学评估。在单独的实验中，向DT处理的小鼠给予抗PD-L1抗体（α PD-L1; 500 μg，i. p.）博来霉素给药前的预防性治疗。与对照组相比，接受紧急骨髓生成诱导的小鼠显示出更严重的PH、右心室重塑和肺血管肌肉化，而肺纤维化没有变化。PH恶化与肺髓源性抑制细胞（MDSC）增加相关，特别是多形核MDSC（PMN-MDSC）。α PD-L1治疗使肺动脉压正常化。同样发现PD-L1表达在来自患有间质性肺病和PH的患者的循环PMN-MDSC上升高。PD-L1是PH中可行的治疗靶点，通过涉及MDSC的信号传导轴起作用。这篇文章是关于心脏保护中的风险因素、合并症和合并症的主题问题的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc
Pulmonary hypertension (PH) secondary to chronic lung disease (World Health Organization Group 3 PH) is deadly, with lung transplant being the only available long‐term treatment option. Myeloid‐derived cells are known to affect progression of both pulmonary fibrosis and PH, although the mechanism of action is unknown. Therefore, we investigated the effect of myeloid cell proliferation induced by emergency myelopoiesis on development of PH and therapy directed against programmed death‐ligand 1 (PD‐L1), expressed by myeloid cells in prevention of pulmonary vascular remodelling. LysM.Cre‐DTR (“mDTR”) mice were injected with bleomycin (0.018 U·g−1, i.p.) while receiving either vehicle or diphtheria toxin (DT; 100 ng, i.p.) to induce severe PH. Approximately 4 weeks after initiation of bleomycin protocol, right ventricular pressure measurements were performed and tissue samples collected for histologic assessment. In a separate experiment, DT‐treated mice were given anti‐PD‐L1 antibody (αPD‐L1; 500 μg, i.p.) preventive treatment before bleomycin administration. Mice undergoing induction of emergency myelopoiesis displayed more severe PH, right ventricular remodelling and pulmonary vascular muscularization compared to controls, without a change in lung fibrosis. This worsening of PH was associated with increased pulmonary myeloid‐derived suppressor cell (MDSC), particularly polymorphonuclear MDSC (PMN‐MDSC). Treatment with αPD‐L1 normalized pulmonary pressures. PD‐L1 expression was likewise found to be elevated on circulating PMN‐MDSC from patients with interstitial lung disease and PH. PD‐L1 is a viable therapeutic target in PH, acting through a signalling axis involving MDSC. This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc
登录
查看更多内容
影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
较低的DHEA-S水平可以预测特发性，结缔组织疾病和先天性心脏病相关的肺动脉高压的绝经后妇女的疾病和恶化。
DOI：
10.1183/13993003.00467-2018
发表时间：
2018-06
期刊：
The European respiratory journal
影响因子：
--
作者：
Baird GL;Archer-Chicko C;Barr RG;Bluemke DA;Foderaro AE;Fritz JS;Hill NS;Kawut SM;Klinger JR;Lima JAC;Mullin CJ;Ouyang P;Palevsky HI;Palmisicano AJ;Pinder D;Preston IR;Roberts KE;Smith KA;Walsh T;Whittenhall M;Ventetuolo CE
通讯作者：
Ventetuolo CE
影响因子：
17.1
作者：
Highfill SL;Cui Y;Giles AJ;Smith JP;Zhang H;Morse E;Kaplan RN;Mackall CL
通讯作者：
Mackall CL
DOI：
10.1007/978-1-4939-7837-3_22
发表时间：
2018
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Hua L;Shi J;Shultz LD;Ren G
通讯作者：
Ren G
影响因子：
16.6
作者：
Bronte V;Brandau S;Chen SH;Colombo MP;Frey AB;Greten TF;Mandruzzato S;Murray PJ;Ochoa A;Ostrand-Rosenberg S;Rodriguez PC;Sica A;Umansky V;Vonderheide RH;Gabrilovich DI
通讯作者：
Gabrilovich DI