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Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease

Cellular & Molecular Immunology volume 20, pages 38–50 (2023)Cite this article

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Abstract

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

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Acknowledgements

We thank the Laboratory Animal Center, College of Medicine, National Cheng Kung University and Taiwan Animal Consortium for the technical support in IVIS.

Funding

This work was supported by the Ministry of Science and Technology (MOST) of Taiwan (grant numbers 103-2321-B-006-030 and 104-2321-B-006-008), funding received in part from the Headquarters of University Advancement at the National Cheng Kung University, which is sponsored by the Ministry of Education in Taiwan, and a research grant (1JA8) from the Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan.

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Authors and Affiliations

  1. Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan, China

    Miao-Hsi Hsieh, Pei-Chi Chen, Wen-Shuo Kuo, Shulhn-Der Wang, Lawrence Shih-Hsin Wu & Jiu-Yao Wang

  2. Graduate Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China

    Miao-Hsi Hsieh

  3. Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan, China

    Pei-Chi Chen & Hui-Fang Kao

  4. Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China

    Han-Yin Hsu, Jui-Chang Liu & Yu-Sheng Ho

  5. Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan, China

    Yuh Jyh Lin

  6. Division of Pulmonary Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China

    Chin-Wei Kuo

  7. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China

    Chin-Wei Kuo

  8. School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing, China

    Wen-Shuo Kuo

  9. School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan, China

    Shulhn-Der Wang

  10. Department of Respirology and Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, China

    Zhi-Gang Liu

  11. Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, China

    Lawrence Shih-Hsin Wu

  12. Department of Allergy, Immunology, and Rheumatology (AIR), China Medical University Children’s Hospital, Taichung, Taiwan, China

    Jiu-Yao Wang

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  1. Miao-Hsi Hsieh
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Contributions

MHH, LSHW, and JYW developed the study concepts and aims. MHH, HYH, JCL, YSH, SDW, and WSK performed the experiments and data extraction. CWK collected the clinical BALF samples from COPD patients. MHH, WSK, HFK, and ZGL performed the data analysis. MHH, LSHW, and JYW drafted the manuscript. All authors provided important insight into data interpretation and contributed to the final version of the manuscript.

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Correspondence to Lawrence Shih-Hsin Wu or Jiu-Yao Wang.

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Hsieh, MH., Chen, PC., Hsu, HY. et al. Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease. Cell Mol Immunol 20, 38–50 (2023). https://doi.org/10.1038/s41423-022-00946-2

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