MHC class I-specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice.
Transfusion-related acute lung injury (TRALI), a form of noncardiogenic pulmonary edema that develops during or within 6 h after a blood transfusion, is the most frequent cause of transfusion-associated death in the United States. Because development of TRALI is associated with donor antibodies (Abs) reactive with recipient major histocompatibility complex (MHC), a mouse model has been studied in which TRALI-like disease is caused by injecting mice with anti-MHC class I monoclonal Ab (mAb). Previous publications with this model have concluded that disease is caused by FcR-dependent activation of neutrophils and platelets, with production of reactive oxygen species that damage pulmonary vascular endothelium. In this study, we confirm the role of reactive oxygen species in the pathogenesis of this mouse model of TRALI and show ultrastructural evidence of pulmonary vascular injury within 5 min of anti-MHC class I mAb injection. However, we demonstrate that disease induction in this model involves macrophages rather than neutrophils or platelets, activation of complement and production of C5a rather than activation of FcγRI, FcγRIII, or FcγRIV, and binding of anti-MHC class I mAb to non-BM-derived cells such as pulmonary vascular endothelium. These observations have important implications for the prevention and treatment of TRALI.
Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Richard T
RT
Strait
Wyenona
W
Hicks
Nathaniel
N
Barasa
Ashley
A
Mahler
Marat
M
Khodoun
Jörg
J
Köhl
Keith
K
Stringer
David
D
Witte
Nico
N
Van Rooijen
Brian M
BM
Susskind
Fred D
FD
Finkelman
D055371:Acute Lung Injury / Q000209:etiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D003167:Complement Activation / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D006183:H-2 Antigens / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012044:Regression Analysis; D065227:Transfusion Reaction
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D006183:H-2 Antigens; D017382:Reactive Oxygen Species