title: C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury.
abstract: Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress triggered by blood transfusions and is the leading cause of transfusion-related mortality. TRALI has primarily been attributed to passive infusion of HLA and/or human neutrophil antigen antibodies present in transfused blood products, and predisposing factors such as inflammation are known to be important for TRALI initiation. Because the acute-phase protein C-reactive protein (CRP) is highly upregulated during infections and inflammation and can also enhance antibody-mediated responses such as in vitro phagocytosis, respiratory burst, and in vivo thrombocytopenia, we investigated whether CRP affects murine antibody-mediated TRALI induced by the anti-major histocompatibility complex antibody 34-1-2s. We found that BALB/c mice injected with 34-1-2s or CRP alone were resistant to TRALI, however mice injected with 34-1-2s together with CRP had significantly enhanced lung damage and pulmonary edema. Mechanistically, 34-1-2s injection with CRP resulted in a significant synergistic increase in plasma levels of the neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and pulmonary neutrophil accumulation. Importantly, murine MIP-2 is the functional homolog of human interleukin-8, a known risk factor for human TRALI. These results suggest that elevated in vivo CRP levels, like those observed during infections, may significantly predispose recipients to antibody-mediated TRALI reactions and support the notion that modulating CRP levels is an effective therapeutic strategy to reduce TRALI severity.
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and.
authors.forename: Rick
authors.initials: R
authors.lastname: Kapur
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and.
authors.forename: Shanjeevan
authors.initials: S
authors.lastname: Shanmugabhavananthan
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada;
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and Departments of Pharmacology, Medicine, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects / Q000276:immunology; D002097:C-Reactive Protein / Q000276:immunology*; D004195:Disease Models, Animal; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D065227:Transfusion Reaction
chemical_list: D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D002097:C-Reactive Protein