Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies
| Autor: | Heike Berghöfer, Sentot Santoso, Jürgen Bux, Behnaz Bayat, Wiebke Wasel, Ulrich J. Sachs, Gregor Bein, Angelika Reil, Katja Hattar, Norbert Weissmann, Rainer M. Bohle |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Isoantigens medicine.medical_specialty Neutrophils Acute Lung Injury Immunology Cell Separation Human leukocyte antigen Lung injury Biochemistry Monocytes Neutrophil Activation Capillary Permeability Pathogenesis Antigen Isoantibodies Internal medicine Animals Humans Medicine Hematology biology business.industry Monocyte Histocompatibility Antigens Class II Transfusion Reaction Cell Biology Flow Cytometry medicine.disease Rats medicine.anatomical_structure biology.protein Female Antibody business Transfusion-related acute lung injury |
| Zdroj: | Blood. 117:669-677 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2010-05-286146 |
| Popis: | Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II–induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody–dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibody–induced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures. |
| Databáze: | OpenAIRE |
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