title: Platelets are dispensable for antibody-mediated transfusion-related acute lung injury in the mouse.
abstract: Essentials Role of platelets in immunological transfusion-related acute lung injury (TRALI) is debated. Immunological TRALI was tested in mice exhibiting severe thrombocytopenia or platelet dysfunction. Platelets are required to prevent lung hemorrhage but not edema formation and respiratory distress. Platelets are dispensable for the initiation and development of TRALI.
  
  
  
  Background Transfusion-related acute lung injury (TRALI) is a serious transfusion-related complication. Previous conflicting studies have indicated that platelets are either crucial or dispensable for TRALI. Objectives To evaluate the role of platelets in major histocompatibility complex (MHC) I-induced-TRALI. Methods Antibody-mediated TRALI was experimentally induced in mice by lipopolysaccharide priming followed by the administration of an anti-MHC I mAb. Results TRALI was tested in the context of severe thrombocytopenia provoked by the administration of diphtheria toxin (DT) in transgenic iDTR mice selectively expressing DT receptor in megakaryocytes. The pathologic responses occurring within the first 10 min following the injection of the anti-MHC I mAb, i.e. the severity of lung edema and the drop in aortic blood oxygenation, were similar in severely thrombocytopenic DT-iDTR and control mice. At later times, mortality was nevertheless increased in DT-iDTR mice, owing to lung hemorrhages. When less severe thrombocytopenia was induced with an antiplatelet mAb, TRALI started and developed similarly as in control mice, but hemorrhages were absent. Furthermore, when platelet functions were defective because of administration of aspirin or clopidogrel, or because of glycoprotein (GP)IIbIIIa deficiency, TRALI still developed but no lung hemorrhages were observed. In contrast, when GPVI was immunodepleted, TRALI still occurred, but was occasionally accompanied by hemorrhages. Conclusions Platelets are dispensable for the initiation and development of MHC I-induced TRALI. Although they do not protect against the disruption of the vascular endothelial cell barrier and the subsequent plasma leakage and edema formation, platelets are essential to prevent more serious damage resulting in hemorrhages in alveoli.
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Hechler
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Maître
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Magnenat
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: V
authors.initials: V
authors.lastname: Heim
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: M-B
authors.initials: MB
authors.lastname: El Mdawar
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Gachet
authors.affiliation: UMR_S949, INSERM, Strasbourg, France.|Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: H
authors.initials: H
authors.lastname: de la Salle
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D001803:Blood Transfusion; D000077144:Clopidogrel; D004167:Diphtheria Toxin; D004487:Edema / Q000473:pathology; D006470:Hemorrhage / Q000188:drug therapy; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008533:Megakaryocytes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000097:blood; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000188:drug therapy / Q000235:genetics; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000073617:Transfusion-Related Acute Lung Injury / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D004167:Diphtheria Toxin; D015395:Histocompatibility Antigens Class I; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: acute lung injury; blood platelets; blood transfusion; hemorrhage; pulmonary edema; thrombocytopenia