Macrophages: Friend or Foe in Idiopathic Pulmonary Fibrosis?

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2018 Sep 8

PMID 30189872

Citations 166

Authors

Lei Zhang

Yi Wang

Guorao Wu

Weining Xiong

Weikuan Gu

Cong-Yi Wang

Affiliations

Soon will be listed here.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a prototype of lethal, chronic, progressive interstitial lung disease of unknown etiology. Over the past decade, macrophage has been recognized to play a significant role in IPF pathogenesis. Depending on the local microenvironments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) phenotypes. In general, M1 macrophages are responsible for wound healing after alveolar epithelial injury, while M2 macrophages are designated to resolve wound healing processes or terminate inflammatory responses in the lung. IPF is a pathological consequence resulted from altered wound healing in response to persistent lung injury. In this review, we intend to summarize the current state of knowledge regarding the process of macrophage polarization and its mediators in the pathogenesis of pulmonary fibrosis. Our goal is to update the understanding of the mechanisms underlying the initiation and progression of IPF, and by which, we expect to provide help for developing effective therapeutic strategies in clinical settings.

Citing Articles

Insights into CSF-1/CSF-1R signaling: the role of macrophage in radiotherapy.

Shang Q, Zhang P, Lei X, Du L, Qu B Front Immunol. 2025; 16:1530890.

PMID: 40007537 PMC: 11851012. DOI: 10.3389/fimmu.2025.1530890.

PET Imaging of CD206 Macrophages in Bleomycin-Induced Lung Injury Mouse Model.

Tekin V, Zhang Y, Yates C, Jaynes J, Lopez H, Garvin C Pharmaceutics. 2025; 17(2).

PMID: 40006620 PMC: 11860134. DOI: 10.3390/pharmaceutics17020253.

Discoid Domain Receptors Signaling in Macrophages-Mediated Diseases.

Ma Y, Gong H, Cheng L, Zhang D Int J Gen Med. 2025; 18:907-926.

PMID: 39990299 PMC: 11847422. DOI: 10.2147/IJGM.S487093.

Reducing M2 macrophage in lung fibrosis by controlling anti-M1 agent.

Bahram Yazdroudi F, Malek A Sci Rep. 2025; 15(1):4120.

PMID: 39900943 PMC: 11791193. DOI: 10.1038/s41598-024-76561-0.

USP25 stabilizes STAT6 to promote IL-4-induced macrophage M2 polarization and fibrosis.

Xu Y, Liu J, Wang J, Wang J, Lan P, Wang T Int J Biol Sci. 2025; 21(2):475-489.

PMID: 39781451 PMC: 11705635. DOI: 10.7150/ijbs.99345.

References

Van Dyken S, Locksley R . Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013; 31:317-43. PMC: 3606684. DOI: 10.1146/annurev-immunol-032712-095906. View

Samara K, Antoniou K, Karagiannis K, Margaritopoulos G, Lasithiotaki I, Koutala E . Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis. Int J Oncol. 2012; 40(5):1397-404. DOI: 10.3892/ijo.2012.1374. View

Ji W, Ma Y, Zhou X, Zhang Y, Lu R, Guo Z . Spironolactone attenuates bleomycin-induced pulmonary injury partially via modulating mononuclear phagocyte phenotype switching in circulating and alveolar compartments. PLoS One. 2013; 8(11):e81090. PMC: 3834272. DOI: 10.1371/journal.pone.0081090. View

Shivshankar P, Halade G, Calhoun C, Escobar G, Mehr A, Jimenez F . Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction. J Mol Cell Cardiol. 2014; 76:84-93. PMC: 4533121. DOI: 10.1016/j.yjmcc.2014.07.020. View

Kropski J, Lawson W, Young L, Blackwell T . Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis. Dis Model Mech. 2012; 6(1):9-17. PMC: 3529334. DOI: 10.1242/dmm.010736. View

Sun L, Louie M, Vannella K, Wilke C, LeVine A, Moore B . New concepts of IL-10-induced lung fibrosis: fibrocyte recruitment and M2 activation in a CCL2/CCR2 axis. Am J Physiol Lung Cell Mol Physiol. 2010; 300(3):L341-53. PMC: 3064283. DOI: 10.1152/ajplung.00122.2010. View

Burman A, Tanjore H, Blackwell T . Endoplasmic reticulum stress in pulmonary fibrosis. Matrix Biol. 2018; 68-69:355-365. PMC: 6392005. DOI: 10.1016/j.matbio.2018.03.015. View

Biswas S, Mantovani A . Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010; 11(10):889-96. DOI: 10.1038/ni.1937. View

Sica A, Mantovani A . Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012; 122(3):787-95. PMC: 3287223. DOI: 10.1172/JCI59643. View

10.

Rosas I, Richards T, Konishi K, Zhang Y, Gibson K, Lokshin A . MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med. 2008; 5(4):e93. PMC: 2346504. DOI: 10.1371/journal.pmed.0050093. View

11.

Osterholzer J, Olszewski M, Murdock B, Chen G, Erb-Downward J, Subbotina N . Implicating exudate macrophages and Ly-6C(high) monocytes in CCR2-dependent lung fibrosis following gene-targeted alveolar injury. J Immunol. 2013; 190(7):3447-57. PMC: 3608799. DOI: 10.4049/jimmunol.1200604. View

12.

Lawson W, Grant S, Ambrosini V, Womble K, Dawson E, Lane K . Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004; 59(11):977-80. PMC: 1746860. DOI: 10.1136/thx.2004.026336. View

13.

Yona S, Kim K, Wolf Y, Mildner A, Varol D, Breker M . Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013; 38(1):79-91. PMC: 3908543. DOI: 10.1016/j.immuni.2012.12.001. View

14.

Tian S, Zhang L, Tang J, Guo X, Dong K, Chen S . HMGB1 exacerbates renal tubulointerstitial fibrosis through facilitating M1 macrophage phenotype at the early stage of obstructive injury. Am J Physiol Renal Physiol. 2014; 308(1):F69-75. PMC: 4281691. DOI: 10.1152/ajprenal.00484.2014. View

15.

Joshi A, Raymond T, Coelho A, Kunkel S, Hogaboam C . A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to Toll-like receptor agonists. J Leukoc Biol. 2007; 83(2):314-24. DOI: 10.1189/jlb.1007689. View

16.

Fingerlin T, Murphy E, Zhang W, Peljto A, Brown K, Steele M . Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013; 45(6):613-20. PMC: 3677861. DOI: 10.1038/ng.2609. View

17.

Ji W, Ma Y, Zhou X, Zhang Y, Lu R, Sun H . Temporal and spatial characterization of mononuclear phagocytes in circulating, lung alveolar and interstitial compartments in a mouse model of bleomycin-induced pulmonary injury. J Immunol Methods. 2013; 403(1-2):7-16. DOI: 10.1016/j.jim.2013.11.012. View

18.

He C, Larson-Casey J, Gu L, Ryan A, Murthy S, Carter A . Cu,Zn-Superoxide Dismutase-Mediated Redox Regulation of Jumonji Domain Containing 3 Modulates Macrophage Polarization and Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2015; 55(1):58-71. PMC: 4942206. DOI: 10.1165/rcmb.2015-0183OC. View

19.

Zhang H, Han G, Liu H, Chen J, Ji X, Zhou F . The development of classically and alternatively activated macrophages has different effects on the varied stages of radiation-induced pulmonary injury in mice. J Radiat Res. 2011; 52(6):717-26. DOI: 10.1269/jrr.11054. View

20.

Wang Q, Ni H, Lan L, Wei X, Xiang R, Wang Y . Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages. Cell Res. 2010; 20(6):701-12. DOI: 10.1038/cr.2010.52. View