The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 8: 1407 - 1414

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.08.014

Treatise：Mechanism Exploration

Dynamic changes of immune cell subsets in a mouse model of Sugen-hypoxia-induced pulmonary hypertension

  • Jie LIU ,
  • Xin XUE ,
  • Yu GUO ,
  • Zhenqiang GAO ,
  • Hanxiao ZHANG ,
  • Muzhi ZHANG ,
  • Huanyu LONG ,
  • Jialu Lü ,
  • Mengyu XU ,
  • Yufeng JIA ,
  • Ye CUI ,
  • Wei WANG ,
  • Ying SUN ,
  • Lei WANG
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  • 1.Department of Immunology，School of Basic Medical Sciences，Capital Medical University，Beijing 100069，Beijing，China
    2.Department of Respiratory and Critical Care Medicine，the Second Affiliated Hospital of Xi'an Jiaotong University，Shaanxi 710004，Xi'an，China
    3Department of Respiratory and Critical Care Medicine，Peking University Third Hospital，Beijing 100191，Beijing，China

Received date: 2025-11-06

  Online published: 2026-04-28

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Abstract

Objective To investigate the dynamic changes of immune cell subsets in a mouse model of pulmonary hypertension （PH） induced by Sugen-hypoxia （SuHx）. Methods A SuHx-PH mouse model was established through intraperitoneal injection of Sugen 5416， followed by exposure to hypoxia. Mouse lung tissues were collected prior to modeling and at 1 week （h1w）， 2 weeks （h2w）， 3 weeks （h3w）， and 4 weeks （h4w） post-modeling. Flow cytometry was employed to detect the proportional alterations of immune cell subsets （including T cells， B cells， macrophages， eosinophils （EOS）， neutrophils （Neu）， natural killer （NK） cells， and innate lymphoid cells （ILCs） within CD45+ immune cells. Results Compared with the control group， the immune cell subsets in SuHx model mice demonstrated significant temporal changes. Among these， the total CD11c+F4/80+ macrophages and interstitial macrophages （IM， SIGLECF-） showed a significant decreasing tendency as the modeling time progressed； the cell levels of alveolar macrophages （AM， SIGLECF+） continuously increased （P < 0.05）； EOS， ILCs， Neu， and CD4+T cells displayed a significant fluctuating pattern， with significant differences between groups （P < 0.05）. Conclusions The proportions of immune cell subsets in the lung tissues of SuHx-PH mice exhibit significant temporal changes， indicating that different immune cells may play stage-specific roles in the progression of PH. This study offers a foundation for a more in-depth understanding of the immunoinflammatory mechanism of PH and the identification of potential immune intervention targets.

Key words： Sugen-hypoxia model; pulmonary hypertension; immune cells; flow cytometry

Cite this article

Jie LIU , Xin XUE , Yu GUO , Zhenqiang GAO , Hanxiao ZHANG , Muzhi ZHANG , Huanyu LONG , Jialu Lü , Mengyu XU , Yufeng JIA , Ye CUI , Wei WANG , Ying SUN , Lei WANG . Dynamic changes of immune cell subsets in a mouse model of Sugen-hypoxia-induced pulmonary hypertension[J]. The Journal of Practical Medicine, 2026 , 42(8) : 1407 -1414 . DOI: 10.3969/j.issn.1006-5725.2026.08.014

References

[1] TUDER R M. Pulmonary vascular remodeling in pulmonary hypertension［J］. Cell Tissue Res， 2017， 367（3）： 643-649. doi：10.1007/s00441-016-2539-y .
[2] 罗志梅， 刘虹延， 孙得胜. 一种肺血管基因敲减动物模型的构建及在肺动脉高压中的运用［J］. 实用医学杂志， 2023， 39（4）： 404-409. doi：10.3969/j.issn.1006-5725.2023.04.003 .
[3] 张嘉莹， 樊勇， 张卓莉. 肺动脉高压发病机制中的肺血管重塑［J］. 中华临床免疫和变态反应杂志， 2023， 17（1）： 50-55. doi：10.3969/j.issn.1673-8705.2023.01.010 .
[4] 徐明艳， 韩校鹏， 刘英丽， 等. 慢性阻塞性肺疾病急性加重期并发肺动脉高压的危险因素［J］. 实用医学杂志， 2022， 38（19）： 2467-2471.doi：10.3969/j.issn.1006-5725.2022.19.017 .
[5] ZAWIA A， ARNOLD N D， WEST L， et al. Altered macrophage polarization induces experimental pulmonary hypertension and is observed in patients with pulmonary arterial hypertension［J］. Arterioscler Thromb Vasc Biol， 2021， 41（1）： 430-445. doi：10.1161/ATVBAHA.120.314639 .
[6] LI C， LIU P， SONG R， et al. Immune cells and autoantibodies in pulmonary arterial hypertension［J］. Acta Biochim Biophys Sin， 2017， 49（12）： 1047-1057. doi：10.1093/abbs/gmx095 .
[7] TARASEVICIENE-STEWART L， KASAHARA Y， ALGER L， et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension［J］. FASEB J， 2001， 15（2）： 427-438. doi：10.1096/fj.00-0343com .
[8] 陈子宜，孙红燕，康品方，等.肺动脉高压动物实验模型的研究进展［J/OL］.实验动物与比较医学，1-18［2026-03-02］..
[9] COSSARIZZA A， CHANG H D， RADBRUCH A， et al. Guidelines for the use of flow cytometry and cell sorting in immunological studies （second edition）［J］. Eur J Immunol， 2019， 49（10）： 1457-1973. doi：10.1002/eji.201970107 .
[10] SORKHDINI P， KLUBOCK-SHUKLA K， SHETH S， et al. Type 2 innate immunity promotes the development of pulmonary fibrosis in Hermansky-Pudlak syndrome［J］. JCI Insight， 2024， 9（22）： e178381. doi：10.1172/jci.insight.178381 .
[11] IKUTANI M， SHIMIZU S， OKADA K， et al. Characterization of long-term interleukin-33 administration as an animal model of pulmonary arterial hypertension［J］. Biochem Biophys Res Commun， 2024， 734： 150750. doi：10.1016/j.bbrc.2024.150750 .
[12] LI N， LI Q， BAI J， et al. The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia［J］. Cell Stress Chaperones， 2020， 25（5）： 779-791. doi：10.1007/s12192-020-01117-w .
[13] SERHAN C N， BRAIN S D， BUCKLEY C D， et al. Resolution of inflammation： State of the art， definitions and terms［J］. FASEB J， 2007， 21（2）： 325-332. doi：10.1096/fj.06-7227rev .
[14] KUANG M， CHEN Y， XING Y， et al. Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model［J］. Respir Res， 2023， 24（1）： 202. doi：10.1186/s12931-023-02501-7 .
[15] 秦崇， 潘磊， 李佳， 等. 低压低氧肺动脉高压形成中CD4+T细胞亚群的变化［J］. 标记免疫分析与临床， 2024， 31（9）： 1580-1588. doi：10.11748/bjmy.issn.1006-1703.2024.09.003 .
[16] AYASS M A， TRIPATHI T， ZHU K， et al. T helper （Th） cell profiles and cytokines/chemokines in characterization， treatment， and monitoring of autoimmune diseases［J］. Methods， 2023， 220： 115-125. doi：10.1016/j.ymeth.2023.11.003 .
[17] TAMOSIUNIENE R， MANOUVAKHOVA O， MESANGE P， et al. Dominant role for regulatory T cells in protecting females against pulmonary hypertension［J］. Circ Res， 2018， 122（12）： 1689-1702. doi：10.1161/CIRCRESAHA.117.312058 .
[18] SHU T， ZHANG J， ZHOU Y， et al. Eosinophils protect against pulmonary hypertension through 14-HDHA and 17-HDHA［J］. Eur Respir J， 2023， 61（3）： 2200582. doi：10.1183/13993003.00582-2022 .
[19] 陈睿迪， 王炜， 张若旸. 巨噬细胞在间质性肺疾病相关肺动脉高压中的作用［J］. 微生物学免疫学进展， 2025， 53（4）： 87-93. doi：10.13309/j.cnki.pmi.2025.04.014 .
[20] SHAPOURI-MOGHADDAM A， MOHAMMADIAN S， VAZINI H， et al. Macrophage plasticity， polarization， and function in health and disease［J］. J Cell Physiol， 2018， 233（9）： 6425-6440. doi：10.1002/jcp.26429 .
[21] ZHANG M Q， WANG C C， PANG X B， et al. Role of macrophages in pulmonary arterial hypertension［J］. Front Immunol， 2023， 14： 1152881. doi：10.3389/fimmu.2023.1152881 .
[22] FLORENTIN J， COPPIN E， VASAMSETTI S B， et al. Inflammatory macrophage expansion in pulmonary hypertension depends upon mobilization of blood-borne monocytes［J］. J Immunol， 2018， 200（10）： 3612-3625. doi：10.4049/jimmunol.1701287 .
[23] AL-QAZAZI R， LIMA P D A， PRISCO S Z， et al. Macrophage-NLRP3 activation promotes right ventricle failure in pulmonary arterial hypertension［J］. Am J Respir Crit Care Med， 2022， 206（5）： 608-624. doi：10.1164/rccm.202110-2274OC .
[24] DANG B， GAO Q， ZHANG L， et al. The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages［J］. Cell Rep， 2023， 42（5）： 112471. doi：10.1016/j.celrep.2023.112471 .
[25] NIE X， SHEN C， TAN J， et al. Periostin： A potential therapeutic target for pulmonary hypertension？［J］. Circ Res， 2020， 127（9）： 1138-1152. doi：10.1161/CIRCRESAHA.120.316943 .
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