Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI

Abstract

Abstract 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.