Novel swine model of transfusion-related acute lung injury
- This study was partially supported by a grant from the Ministry of Health, Labour and Welfare 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 diagnosis and treatment of severe adverse events of transfusion such as TRALI and TACO”).
Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion. 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 developed, 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 leukocyte 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.
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 significantly decreased (p < 0.05). Bilateral infiltration was shown in chest X-ray imaging. Lung injury was confirmed by histopathologic analysis.
Lung injury in pigs was successfully induced by anti-SLA MoAb. Priming with LPS is a prerequisite for inducing lung injury and the amount of the antibody is a critical condition.