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MURINE MODEL OF TRANSFUSION RELATED ACUTE LUNG INJURY (TRALI) DUE TO ANTI-MHC.
Richard T. Strait, MD , Wyenona Hicks BS , Brian M. Susskind, PhD and Fred D. Finkelman, MD . Cincinnati Children
s Hospital Medical Center, 45229, Emergency Medicine and Immunology ; Cincinnati Hoxworth Blood Center, 45267, Transplantation Immunology Division and Cincinnati U Cincinnati College of Medicine, 45267, Immunology- Internal Medicine .
TRALI, the 3rd most common life threatening complication of blood transfusion, is caused in part by anti-HLA antibodies.. To help elucidate pathogenic mechanisms of TRALI, we endeavored to develop a murine model. BALB/c (H-2d) or congenic mice (H2k) were iv challenged (5/grp) with a mouse IgG2a anti-mouse H2 Kd/Dd monoclonal antibody, 34-1-2s, and core temperatures followed. Some mice were pretreated with a rat IgG2a anti-FcγRII/III mAb (24G2), PAF antagonist (CV6209) or gadolinium. Temperature drop over the first 30 minutes of mice challenged with 34-1-2s was > 3°C, with recovery to normal temperature over next 30 to 90 minutes; congenic mice had no response to the challenge, demonstrating a specificity to the reaction to the antibody (Fig 1). Partial dependence on macrophages and PAF was shown by a marked inhibition of temperature drop by pretreatment with gadolinium or CV6209, respectively. Pretreatment with 24G2 completely inhibited temperature drop, suggestive of dependence on FcγRIII in this model. These studies suggest that IgG, FcγRIII, macrophages and PAF may be important in anaphylactic responses to anti-MHC antibodies. Presence of FcγRIII on human macrophages makes it possible that IgG, FcγRIII, macrophages, and PAF also contributes to human TRALI immonopathology. This animal model may be useful in elucidating TRALI pathogenesis, as well as identification of co-morbid factors and therapeutic interventions.