Mechanism and intervention of murine transfusion-related acute lung injury caused by anti-CD36 antibodies

Chen, Da-Wei, Kang, Tian, Xu, Xiu-Zhang, Xia, Wen-Jie, Ye, Xin, Wu, Yong-Bin, Xu, Yao-Ri, Liu, Jing, Ren, Hui, Deng, Jing, Chen, Yang-Kai, Ding, Hao-Qiang, Aslam, Muhammad, Zelek, Wioleta M., Morgan, B. Paul, Kapur, Rick, Santoso, Sentot and Fu, Yong-Shui 2023. Mechanism and intervention of murine transfusion-related acute lung injury caused by anti-CD36 antibodies. JCI Insight 8 (6) , e165142. 10.1172/jci.insight.165142

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Abstract

Anti-CD36 Abs have been suggested to induce transfusion-related acute lung injury (TRALI) upon blood transfusion, particularly in Asian populations. However, little is known about the pathological mechanism of anti-CD36 Ab–mediated TRALI, and potential therapies have not yet been identified. Here, we developed a murine model of anti-CD36 Ab–mediated TRALI to address these questions. Administration of mouse mAb against CD36 (mAb GZ1) or human anti-CD36 IgG, but not GZ1 F(ab′)2 fragments, induced severe TRALI in Cd36+/+ male mice. Predepletion of recipient monocytes or complement, but not neutrophils or platelets, prevented the development of murine TRALI. Moreover, plasma C5a levels after TRALI induction by anti-CD36 Abs increased more than 3-fold, implying a critical role of complement C5 activation in the mechanism of Fc-dependent anti-CD36–mediated TRALI. Administration of GZ1 F(ab′)2, antioxidant (N-acetyl cysteine, NAC), or C5 blocker (mAb BB5.1) before TRALI induction completely protected mice from anti-CD36–mediated TRALI. Although no significant amelioration in TRALI was observed when mice were injected with GZ1 F(ab′)2 after TRALI induction, significant improvement was achieved when mice were treated postinduction with NAC or anti-C5. Importantly, anti-C5 treatment completely rescued mice from TRALI, suggesting the potential role of existing anti-C5 drugs in the treatment of patients with TRALI caused by anti-CD36.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Society for Clinical Investigation
ISSN:	2379-3708
Date of First Compliant Deposit:	3 April 2023
Date of Acceptance:	15 February 2023
Last Modified:	03 May 2023 16:16
URI:	https://orca.cardiff.ac.uk/id/eprint/158351

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