TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina YazdanbakhshUpdate on the pathophysiology of transfusion-related acute lung injuryZeeuw van der Laan, Eveline A.N.a; van der Velden, Saskiaa; Porcelijn, Leendertb; Semple, John W.c; van der Schoot, C. Ellena; Kapur, RickaAuthor Information aSanquin Research, Department of Experimental Immunohematology, Amsterdam and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam bDepartment of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, the Netherlands cDivision of Hematology and Transfusion Medicine, Lund University, Lund, Sweden Correspondence to Rick Kapur, Department of Experimental Immunohematology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands. Tel: +31 6 45 282 659; e-mail: [email protected] Current Opinion in Hematology: November 2020 - Volume 27 - Issue 6 - p 386-391 doi: 10.1097/MOH.0000000000000607 Buy Metrics Abstract Purpose of review The aim of this study was to discuss recent advances regarding the pathogenesis of transfusion-related acute lung injury (TRALI), which highlight the pathogenic role of macrophages. Recent findings TRALI remains a leading cause of transfusion-related fatalities, despite the success of the mitigation strategy, and therapeutic approaches are unavailable. Neutrophils (PMNs) are recognized pathogenic cells in TRALI. Macrophages have previously also been suggested to be pathogenic in mice via binding of C5a to their C5a-receptor, producing reactive oxygen species (ROS), which damages the pulmonary endothelium. Recent work has further highlighted the role of macrophages in the TRALI-pathogenesis. It has been shown that the protein osteopontin (OPN) released by macrophages is critical for pulmonary PMN recruitment in mice suffering from TRALI and that targeting OPN prevents the occurrence of TRALI. Another recent study demonstrated the importance of M1-polarized alveolar macrophages in murine TRALI induction by showing that α1-antitrypsin (AAT) overexpression prevented TRALI in mice through decreasing the polarization of alveolar macrophages towards the M1 phenotype. Summary Apart from PMNs, macrophages also appear to be important in the pathogenesis of TRALI. Targeting the pathogenic functions of macrophages may be a promising therapeutic strategy to explore in TRALI. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.