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PATHOGENESIS OF TRANSFUSION RELATED ACUTE LUNG INJURY (TRALI) IN AN IN VIVO MURINE MODEL.
Wyenona Hicks, M.S., Brian M. Susskind, Ph.D., Richard Strait, M.D. and Fred Finkelman, M.D.. Cincinnati OH, USA, Hoxworth Blood Center, 45267, Transplantation Immunology Division; Cincinnati OH, USA, Cincinnati Childrens Hospital Medical Center, 45229-3039, Pediatrics and Cincinnati OH, USA, University of Cincinnati Medical School, 45267-0563, Int Med-Immunology.

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TRALI, one of the most common noninfectious, life-threatening complications of blood transfusion, is associated with the administration of blood that contains anti-MHC (Major Histocompatibility Complex) antibodies. We developed an in vivo murine model of TRALI by injecting BALB/c (H-2^d) mice with 34-1-2s, a murine IgG2a anti-H-2^d monoclonal antibody (mAb). Hypothermia (measured by rectal temperatures) and dyspnea (measured by barometric plethysmography) were rapidly induced in BALB/c mice but not in congenic H-2^k controls. Pathological changes associated with the lungs include the presence of pulmonary edema after anti-MHC mAb challenge. Lung histology performed 2 and 24 hours after anti-MHC mAb challenge demonstrated significant inflammatory changes. Moderate infiltration of proteinacious materials was present at 2 hours, becoming yet more remarkable at 24 hours. While absent in the control, cellular infiltration of the lungs was predominately polymorphonuclear at 2 hours and mononuclear at 24 hours. Pretreatment with anti-FcγRII/III mAb, gadolinium, or PAF, histamine or leukotrienes antagonists, inhibited the induction of the hypothermia and dyspnea observed in this model. These results suggest that IgG, FcγRIII, macrophages, PAF, histamine, and leukotrienes are important in anti-MHC antibody induction of hypothermia and pulmonary dysfunction. This animal model may be useful for determining pathogenic mechanisms of TRALI and for identifying potential therapeutic interventions.