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Autor(en) / Beteiligte
Titel
Comparative analysis of the pathological events involved in immune and non-immune TRALI models
Ist Teil von
  • Vox sanguinis, 2012-11, Vol.103 (4), p.309-321
Ort / Verlag
Oxford, UK: Blackwell Publishing Ltd
Erscheinungsjahr
2012
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
  • Background and Objectives  Transfusion‐related acute lung injury (TRALI) is characterized by leukocyte transmigration and alveolar capillary leakage shortly after transfusion. TRALI pathogenesis has not been fully elucidated. In some cases, the infusion of alloantibodies (immune model), whereas in others the combination of neutrophil priming by proinflammatory molecules with the subsequent infusion of biological response modifiers (BRMs) in the hemocomponent (non‐immune model) have been implicated. Our aim was to compare the pathological events involved in TRALI induced by antibodies or BRMs using murine models. Materials and Methods  In the immune model, human HNA‐2+ neutrophils were incubated in vitro with a monoclonal antibody (anti‐CD177, clone 7D8) directed against the HNA‐2 antigen and injected i.v. in NOD/SCID mice. In the non‐immune model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS) followed by platelet‐activating factor (PAF) infusion 2 h later. Forty minutes after PAF administration, or 6 h after neutrophil injection, lungs were isolated and histological analysis, determination of a variety of cytokines and chemokines including keratinocyte‐derived chemokine (KC), MIP‐2, the interleukins IL‐1β, IL‐6, IL‐8 as well as TNFα, cell influx and alveolar capillary leakage were performed. Results  In both models, characteristic histological findings of TRALI and an increase in KC and MIP‐2 levels were detected. In contrast to the immune model, in the non‐immune model, there was a dramatic increase in IL‐1β and TNFα. However, capillary leakage was only detected if PAF was administrated. Conclusions  Regardless of the triggering event(s), KC, MIP‐2 and integrins participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage when two events are involved.

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