Research progress on the functional role of different types of pulmonary macrophages in inflammatory injury of acute respiratory distress syndrome

doi:10.3877/cma.j.issn.2096-1537.2025.03.012

Abstract

Abstract:

The dysregulated inflammatory response is the primary pathophysiological mechanism underlying the onset of acute respiratory distress syndrome (ARDS) in septic patients. Distinct subpopulations of macrophages, namely monocyte-derived alveolar macrophages (Mo-AMs), tissue-resident alveolar macrophages (TRAMs), and pulmonary interstitial macrophages (PIMs), exhibit disparate functional profiles and exert varying impacts on the development of ARDS. Various therapeutic modalities have been proposed to target the three types of pulmonary macrophages mentioned above, encompassing interventions aimed at curtailing the generation of Mo-AMs, mitigating the hyperactivation of TRAM-mediated inflammation, and augmenting the anti-inflammatory capacities of PIMs. This review critically examines the functional paradigms of these pulmonary macrophage subtypes in the inflammatory pathogenesis of ARDS, thereby delineating avenues for further investigation and therapeutic exploration in ARDS management.

Key words: Acute respiratory distress syndrome, Monocyte-derived alveolar macrophages, Tissue-resident alveolar macrophages, Pulmonary interstitial macrophages, Inflammatory injury

Shiming Li, Tao Liu, Ling Liu, Haibo Qiu. Research progress on the functional role of different types of pulmonary macrophages in inflammatory injury of acute respiratory distress syndrome[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2025, 11(03): 294-298.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2025.03.012

https://icu.cma-cmc.com.cn/EN/Y2025/V11/I03/294

References 51

1	Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries [J]. JAMA, 2016, 315(8): 788-800.
2	Dhaliwal K, Scholefield E, Ferenbach D, et al. Monocytes control second-phase neutrophil emigration in established lipopolysaccharide-induced murine lung injury [J]. Am J Respir Crit Care Med, 2012, 186(6): 514-524.
3	Jiang Z, Zhou Q, Gu C, et al. Depletion of circulating monocytes suppresses IL-17 and HMGB1 expression in mice with LPS-induced acute lung injury [J]. Am J Physiol Lung Cell Mol Physiol, 2017, 312(2): L231-L242.
4	Evren E, Ringqvist E, Willinger T. Origin and ontogeny of lung macrophages: from mice to humans [J]. Immunology, 2020, 160(2): 126-138.
5	Williams H, Mack C, Baraz R, et al. Monocyte differentiation and heterogeneity: inter-subset and interindividual differences [J]. Int J Mol Sci, 2023, 24(10): 8757.
6	Vichare R, Janjic J M. Macrophage-targeted nanomedicines for ARDS/ALI: promise and potential [J]. Inflammation, 2022, 45(6): 2124-2141.
7	Li F, Piattini F, Pohlmeier L, et al. Monocyte-derived alveolar macrophages autonomously determine severe outcome of respiratory viral infection [J]. Sci Immunol, 2022, 7(73): eabj5761.
8	Aegerter H, Kulikauskaite J, Crotta S, et al. Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection [J]. Nat Immunol, 2020, 21(2): 145-157.
9	Gómez-Rial J, Rivero-Calle I, Salas A, et al. Role of monocytes/macrophages in COVID-19 pathogenesis: implications for therapy [J]. Infect Drug Resist, 2020, 13: 2485-2493.
10	Lee J W, Chun W, Lee H J, et al. The role of macrophages in the development of acute and chronic inflammatory lung diseases [J]. Cells, 2021, 10(4): 897.
11	Codo AC, Davanzo GG, Monteiro LB, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis-dependent axis [J]. Cell Metab, 2020, 32(3): 498-499.
12	Theofani E, Semitekolou M, Samitas K, et al. TFEB signaling attenuates NLRP3-driven inflammatory responses in severe asthma [J]. Allergy, 2022, 77(7): 2131-2146.
13	Lazarov T, Juarez-Carreño S, Cox N, et al. Physiology and diseases of tissue-resident macrophages [J]. Nature, 2023, 618(7966): 698-707.
14	Czimmerer Z, Nagy L. Epigenomic regulation of macrophage polarization: Where do the nuclear receptors belong? [J]. Immunol Rev, 2023, 317(1): 152-165.
15	Dong T, Chen X, Xu H, et al. Mitochondrial metabolism mediated macrophage polarization in chronic lung diseases [J]. Pharmacol Ther, 2022, 239: 108208.
16	H etzel M, Ackermann M, Lachmann N. Beyond "big eaters": the versatile role of alveolar macrophages in health and disease [J]. Int J Mol Sci, 2021, 22(7): 3308.
17	Chen S, Saeed A, Liu Q, et al. Macrophages in immunoregulation and therapeutics [J]. Signal Transduct Target Ther, 2023, 8(1): 207.
18	Luo J, Wang J, Zhang J, et al. Nrf2 deficiency exacerbated CLP-induced pulmonary injury and inflammation through autophagy- and NF-κB/PPARγ-mediated macrophage polarization [J]. Cells, 2022, 11(23): 3927.
19	Demkow U. Molecular mechanisms of neutrophil extracellular trap (NETs) degradation [J]. Int J Mol Sci, 2023, 24(5): 4896.
20	Xu F, Ma Y, Huang W, et al. Typically inhibiting USP14 promotes autophagy in M1-like macrophages and alleviates CLP-induced sepsis [J]. Cell Death Dis, 2020, 11(8): 666.
21	Bian Z, Gong Y, Huang T, et al. Deciphering human macrophage development at single-cell resolution [J]. Nature, 2020, 582(7813): 571-576.
22	Evren E, Ringqvist E, Tripathi KP, et al. Distinct developmental pathways from blood monocytes generate human lung macrophage diversity [J]. Immunity, 2021, 54(2): 259-275.
23	Dang W, Tao Y, Xu X, et al. The role of lung macrophages in acute respiratory distress syndrome [J]. Inflamm Res, 2022, 71(12): 1417-1432.
24	Chakarov S, Lim HY, Tan L, et al. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches [J]. Science, 2019, 363(6432): eaau0964.
25	Jafarzadeh A, Chauhan P, Saha B, et al. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: lessons from SARS and MERS, and potential therapeutic interventions [J]. Life Sci, 2020, 257: 118102.
26	Junqueira C, Crespo Â, Ranjbar S, et al. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation [J]. Nature, 2022, 606(7914): 576-584.
27	Janssen WJ, Barthel L, Muldrow A, et al. Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury [J]. Am J Respir Crit Care Med, 2011, 184(5): 547-560.
28	Kadomoto S, Izumi K, Mizokami A. Macrophage polarity and disease control [J]. Int J Mol Sci, 2021, 23(1): 144.
29	Li H, Li Y, Song C, et al. Neutrophil extracellular traps augmented alveolar macrophage pyroptosis via AIM2 inflammasome activation in LPS-induced ALI/ARDS [J]. J Inflamm Res, 2021, 14: 4839-4858.
30	Jiang P, Jin Y, Sun M, et al. Extracellular histones aggravate inflammation in ARDS by promoting alveolar macrophage pyroptosis [J]. Mol Immunol, 2021, 135: 53-61.
31	Wang C, Xie J, Zhao L, et al. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients [J]. EBioMedicine, 2020, 57: 102833.
32	Wu D, Wang Y, Hu J, et al. Rab26 promotes macrophage phagocytosis through regulation of MFN2 trafficking to mitochondria [J]. FEBS J, 2023, 290(16): 4023-4039.
33	Mould KJ, Jackson ND, Henson PM, et al. Single cell RNA sequencing identifies unique inflammatory airspace macrophage subsets [J]. JCI Insight, 2019, 4(5): e126556. .
34	Cheng P, Li S, Chen H. Macrophages in Lung Injury, Repair, and Fibrosis [J]. Cells, 2021, 10(2): 436.
35	Huang X, Xiu H, Zhang S, et al. The Role of Macrophages in the Pathogenesis of ALI/ARDS [J]. Mediators Inflamm, 2018, 2018: 1264913.
36	Wang QL, Yang L, Liu ZL, et al. Sirtuin 6 regulates macrophage polarization to alleviate sepsis-induced acute respiratory distress syndrome via dual mechanisms dependent on and independent of autophagy [J]. Cytotherapy, 2022, 24(2): 149-160.
37	Ural BB, Yeung ST, Damani-Yokota P, et al. Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties [J]. Sci Immunol, 2020, 5(45): eaax8756.
38	Xu J, Wang J, Wang X, et al. Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages [J]. Cell Death Dis, 2020, 11(10): 934.
39	Sun H, Zhang Y, Wang J, et al. Application of lung-targeted lipid nanoparticle-delivered mRNA of soluble PD-L1 via SORT technology in acute respiratory distress syndrome [J]. Theranostics, 2023, 13(14): 4974-4992.
40	Wang H, Tumes DJ, Hercus TR, et al. Blocking the human common beta subunit of the GM-CSF, IL-5 and IL-3 receptors markedly reduces hyperinflammation in ARDS models [J]. Cell Death Dis, 2022, 13(2): 137.
41	Fung NH, Wang H, Vlahos R, et al. Targeting the human βc receptor inhibits inflammatory myeloid cells and lung injury caused by acute cigarette smoke exposure [J]. Respirology, 2022, 27(8): 617-629.
42	Sommer F, Ortiz Zacarı As NV, Heitman LH, et al. Inhibition of macrophage migration in zebrafish larvae demonstrates in vivo efficacy of human CCR2 inhibitors [J]. Dev Comp Immunol, 2021, 116: 103932.
43	Wang S, Bai J, Zhang YL, et al. CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration [J]. Redox Biol, 2022, 56: 102438.
44	Snelgrove RJ, Goulding J, Didierlaurent AM, et al. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection [J]. Nat Immunol, 2008, 9(9): 1074-1083.
45	Xu H, Zhu Y, Hsiao AW, et al. Bioactive glass-elicited stem cell-derived extracellular vesicles regulate M2 macrophage polarization and angiogenesis to improve tendon regeneration and functional recovery [J]. Biomaterials, 2023, 294: 121998.
46	Tang N, Yang Y, Xie Y, et al. CD274 (PD-L1) negatively regulates M1 macrophage polarization in ALI/ARDS [J]. Front Immunol, 2024, 15: 1344805.
47	Tu C, Wang Z, Xiang E, et al. Human umbilical cord mesenchymal stem cells promote macrophage PD-L1 expression and attenuate acute lung injury in mice [J]. Curr Stem Cell Res Ther, 2022, 17(6): 564-575.
48	Mehta P, Porter JC, Manson JJ, et al. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities [J]. Lancet Respir Med, 2020, 8(8): 822-830.
49	Zhou B, Magana L, Hong Z, et al. The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic-epigenetic reprogramming and resolves inflammatory injury [J]. Nat Immunol, 2020, 21(11): 1430-1443.
50	Vanneste D, Bai Q, Hasan S, et al. MafB-restricted local monocyte proliferation precedes lung interstitial macrophage differentiation [J]. Nat Immunol, 2023, 24(5): 827-840.
51	Schyns J, Bai Q, Ruscitti C, et al. Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung [J]. Nat Commun, 2019, 10(1): 3964.

[1]	Xiaolong Zong, Zhiqing Zhou, Jinying Wang, Huiqing Hu, Duanyang Li, Xiao Wang, Yu Sun, Zhenyu Li. Association of bronchoalveolar lavage fluid cathepsin S levels with severity and prognosis of patients with pneumonia-related acute respiratory distress syndrome [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2025, 18(05): 390-396.
[2]	Rong Wu, Zheyi Cai, Yunhua Huang, Jinhai Le, Ping Zhang, Xian Chen, Qiong Yi. Effect of transpulmonary driving pressure guided positive end-expiratory pressure ventilation on pulmonary function and prognosis in patients with acute respiratory distress syndrome [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(06): 866-871.
[3]	Fanglong Shen, Zhengbin Wu, Shifeng Shao, Diyou Chen, Qin Xiao, Zhipeng Hao, Zhen Wang, Hui Zhao, Yaoli Wang. Patterns and predictive value of electrical impedance tomography in patients with acute respiratory distress syndrome [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(06): 897-903.
[4]	Yawen Liu, Yanhu Sun, Xiaohan Xu, Yue Li, Xudong Wang. Clinical analysis of electrical impedance tomography-guided PEEP titration in the treatment of patients with ARDS [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(06): 966-972.
[5]	Xinghua Li, Guixian Li, Ying Liu, Hongyu Geng, Ying Gu, Congcong Han. Effect of combined therapy with silverestana, methylprednisolone sodium succinate, and airway pressure release ventilation on lung function in acute respiratory distress syndrome caused by sepsis [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 789-795.
[6]	Yuqing Lu, Dawei Li, Jianfeng Zou, Zilong Hu, Zhe Li, Qi Li, Liyuan Zhang, Meng Huo, Yue Shen, Weizheng Shuai. Clinical application of the new prone position turning assistance device in patients with acute respiratory distress syndrome [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 757-761.
[7]	Cailin Zhao, Qing Xiang, Hang Qian, Wen Shi, Lingxiao Qiu, Bin Wang. Identification of ferroptosis-related hub genes and immune subtypes in acute lung injury/acute respiratory distress syndrome based on bioinformatics analysis [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(04): 503-509.
[8]	Xue Tian, Dongpo Wei, Xiaoxiao Meng, Hui Xie, Ruilan Wang. Identification of diagnostic biomarkers for acute respiratory distress syndrome-related pulmonary fibrosis based on boinformatics [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(04): 534-539.
[9]	Peng Zhang, Manman Shi, Hui Ma, Jiaojiao Wu, Tun Zhao, Yingbin Zhang. Correlation between the variability of arterial partial pressure of carbon dioxide (PaCO2) and the prognostic risk in patients with acute respiratory distress syndrome (ARDS) during mechanical ventilation [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(02): 226-230.
[10]	Jinlong Wang, Min Shao. Respiratory support technologies：progress and prospects in 2024 [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2025, 11(02): 117-124.
[11]	Lili Huang, Yi Yang, Haibo Qiu. Research progress in mtDNA in lung injury of ARDS patients [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2025, 11(02): 204-209.
[12]	Yunhui Ni, Xueyan Yuan, Lili Huang, Yi Yang, Haibo Qiu. Research progress in respiratory drive in protective ventilation strategy [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2025, 11(01): 91-94.
[13]	Kun Peng, Huibin Feng, Lixue Yuan. Risk factors for acute respiratory distress syndrome in patients with acute organophosphorus pesticide poisoning [J]. Chinese Journal of Clinicians(Electronic Edition), 2025, 19(09): 668-674.
[14]	Linguo Bai, Kangjie Qin, Jie Zheng, Junjie Li, Hong Mei, Xinxin Liu, Song Qin, Banghai Feng, Kun Yu. Forsythiaside A activates PPAR-γ to inhibit neutrophil extracellular traps and alleviate sepsis-associated acute respiratory distress syndrome [J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2025, 11(03): 180-187.
[15]	Fanyan Ou, Qian Guo, Lixiong Zeng, Qiuli Chen, Houyu Gan, Jie Yang. Machine learning and omics-driven dissection of mitophagy and ferroptosis in sepsis-associated ARDS： unraveling key genetic roles and immune regulatory mechanisms [J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2025, 11(02): 86-101.

Please choose a citation manager

Content to export