Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI
Transfusion-related acute lung injury (TRALI) is a leading cause of blood transfusion-triggered mortality. Recently, we demonstrated the critical role of Fc-dependent complement activation in anti-CD36-mediated murine TRALI. In this study, we found that C5-/- mice were protected, and administration of anti-C5 rescued wild-type mice from anti-CD36-mediated TRALI. However, C5aR1-/- mice were not protected against anti-CD36-mediated TRALI, implying a possible role of C5b-9 (membrane attack complex [MAC]). Accordingly, elevated levels of MAC were detected in bronchoalveolar lavage fluid and lung tissue of mice with anti-CD36-induced TRALI. Inhibition of MAC formation by administration of anti-C7-blocking monoclonal antibody alleviated TRALI in mice, suggesting the critical role of the MAC in the pathology of anti-CD36-mediated TRALI. Furthermore, anti-C7 treatment also led to favorable outcome in murine TRALI induced by anti-major histocompatibility complex class 1, indicating the potential broader applicability of MAC inhibitors in the treatment of antibody-mediated TRALI. Therefore, this approach may be promising to further explore the treatment of patients with TRALI.
Authors
- Sentot Santoso (ORCID: https://orcid.org/0000-0001-6943-3945)
- Rick Kapur (ORCID: https://orcid.org/0000-0002-1608-876X)
- Xiuzhang Xu (ORCID: https://orcid.org/0000-0002-1328-6920)
- Hui Ren (ORCID: https://orcid.org/0000-0002-0166-8614)
- Yongshui Fu (ORCID: https://orcid.org/0000-0003-0886-2193)
- Trent M. Woodruff (ORCID: https://orcid.org/0000-0003-1382-911X)
- Yaori Xu (ORCID: https://orcid.org/0000-0002-5498-3554)
- Wenjie Xia (ORCID: https://orcid.org/0000-0002-4681-1947)
- Wioleta M. Zelek (ORCID: https://orcid.org/0000-0002-2230-3550)
- Xin Ye (ORCID: https://orcid.org/0000-0002-6028-2295)
- B. Paul Morgan (ORCID: https://orcid.org/0000-0003-4075-7676)
- Jiansen He (ORCID: https://orcid.org/0000-0001-8179-417X)
- Dawei Chen (ORCID: https://orcid.org/0000-0002-3405-6753)
- Jing Liu (ORCID: https://orcid.org/0000-0001-5588-3865)
- Huaqin Liang
- Shengxue Luo (ORCID: https://orcid.org/0000-0001-7773-7092)
- Yalin Luo
Institutions
- The University of Queensland (AU)
- Justus-Liebig-Universität Gießen (DE)
- Sanquin (NL)
- Guangzhou Blood Center (CN)
- Guangzhou First People's Hospital (CN)
- University of Wales Institute Cardiff (SG)
- Southern Medical University (CN)
- Cardiff University (GB)
- University of Amsterdam (NL)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Blood
- Published
- 2025-05-19
- DOI
- https://doi.org/10.1182/blood.2024028012
- Citations
- 6
- Primary Topic
- Complement system in diseases
- Type
- article
- Field-Weighted Citation Impact
- 4.78
Funders
- National Natural Science Foundation of China