ORIGINAL ARTICLE Novel swine model of transfusion-related acute lung injury Hitoshi Okazaki, 1,3 Osamu Ishikawa, 2 Takehiko Iijima, 3,8 Takahiro Kohira, 1,3 Mai Teranishi, 3 Shin Kawasaki, 4 Akira Saito, 4 Yu Mikami, 4 Asuka Sugiura, 1 Shiho Hashimoto, 1 Eiko Shimada, 1 Makoto Uchikawa, 5 Mika Matsuhashi, 3 Nelson H. Tsuno, 3 Minoru Tanaka, 3 Nobutaka Kiyokawa, 6 Junichiro Fujimoto, 7 Takahide Nagase, 4 Kenji Tadokoro, 1 and Koki Takahashi 3 BACKGROUND: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood trans- fusion. Antibodies against human leukocyte antigens in donors’ plasma are the major causes of TRALI. Several animal models of TRALI have been developed, and the mechanism underlying TRALI development has been extensively investigated using rodent models. Although sheep models of nonimmune TRALI have been devel- oped, large-animal models of antibody-mediated TRALI are not yet available. STUDY DESIGN AND METHODS: To develop a swine model of TRALI, male Clawn strain miniature pigs were used. A monoclonal antibody (MoAb) against swine leu- kocyte antigens (SLAs) Class I (4G8, 0.3 or 1.0 mg/kg body weight [BW]) and a control antibody (1.0 mg/kg BW) were injected into the peripheral vein after priming with or without 1 μg/kg BW lipopolysaccharide (LPS; n = 3 each). Lung injury was assessed using PaO2/FiO2 (P/F) ratio and by chest X-ray imaging. Histopathologic analysis was also conducted. RESULTS: Lung injury could be induced by injecting 4G8 at an amount of 1.0 mg/kg BW, after LPS. The P/F ratio 90 minutes after the administration of 4G8 signifi- cantly decreased (p < 0.05). Bilateral infiltration was shown in chest X-ray imaging. Lung injury was con- firmed by histopathologic analysis. CONCLUSION: Lung injury in pigs was successfully induced by anti-SLA MoAb. Priming with LPS is a pre- requisite for inducing lung injury and the amount of the antibody is a critical condition. T ransfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfu- sion. Currently, the mechanism of TRALI induc- tion is considered to be a two-hit event model. The first hit is the neutrophil priming elicited by the patient’s underlying condition leading neutrophils ABBREVIATIONS: ARDS = acute respiratory distress syndrome; BAL = bronchoalveolar lavage; BW = body weight; LPS = lipopolysaccharide; P/F ratio = PaO2/FiO2 ratio; SLA(s) = swine leukocyte antigen(s). From the 1 Research and Development Department, Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society; the 2 Department of Neurosurgery, the 3 Department of Transfusion Medicine, and the 4 Department of Respiratory Medicine, The University of Tokyo; the 5 Blood Group Section, Japanese Red Cross Kanto-Koshinetsu Block Blood Center; the 6 Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development; and the 7 Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan; and the 8 Department of Anesthesiology, School of Dentistry, Showa University, Showa, Japan. Address reprint requests to: Hitoshi Okazaki, Research and Development Department, Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, 2-1-67 Tatsumi, Koto-ku, Tokyo 135-8521, Japan; e-mail: okazakih-tky@umin.ac.jp. This study was partially supported by a grant from the Ministry of Health, Labour andWelfare of Japan (Research on Regulatory Science of Pharmaceutical and Medical Devices, “Establishing a monitoring system for adverse reaction of blood transfusion” and “Establishing the guideline for the early diag- nosis and treatment of severe adverse events of transfusion such as TRALI and TACO”). Received for publication September 10, 2012; revision received May 19, 2014, and accepted May 20, 2014. doi: 10.1111/trf.12766 © 2014 AABB TRANSFUSION **;**:**-**. Volume **, ** ** TRANSFUSION 1