Beschreibung:
<jats:sec><jats:title>Background</jats:title><jats:p>Human neutrophil alloantigen‐3a (<jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a) antibodies can induce transfusion‐related acute lung injury (<jats:styled-content style="fixed-case">TRALI</jats:styled-content>). The severity of <jats:styled-content style="fixed-case">TRALI</jats:styled-content> varies largely among the affected patients. Severe comorbidity seems to increase the susceptibility for <jats:styled-content style="fixed-case">TRALI</jats:styled-content>, potentially by priming of neutrophils. Thus, the impact of neutrophil priming on <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibody–mediated neutrophil aggregation and <jats:styled-content style="fixed-case">CD</jats:styled-content>11b surface expression was investigated.</jats:p></jats:sec><jats:sec><jats:title>Study Design and Methods</jats:title><jats:p>Neutrophils were primed using formyl‐methionyl‐leucyl‐phenylalanine (<jats:styled-content style="fixed-case">fMLP</jats:styled-content>) or bacterial lipopolysaccharide (<jats:styled-content style="fixed-case">LPS</jats:styled-content>). Granulocyte aggregation and <jats:styled-content style="fixed-case">CD</jats:styled-content>11b surface expression were evaluated by the granulocyte agglutination test and by flow cytometry (<jats:styled-content style="fixed-case">FC</jats:styled-content>), respectively. Priming‐induced changes in the surface expression of choline transporter‐like protein 2 (<jats:styled-content style="fixed-case">CTL</jats:styled-content>2) and the <jats:styled-content style="fixed-case">CTL</jats:styled-content>2 m<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression were assessed by <jats:styled-content style="fixed-case">FC</jats:styled-content> and quantitative real‐time polymerase chain reaction, respectively.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Priming of neutrophils lowered the amount of <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibodies required for inducing granulocyte aggregation in a dose‐dependent manner by 50% to 75%. The priming agent concentration necessary for this response differed between donors. Priming slightly enhanced binding of <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibodies to neutrophils. However, <jats:styled-content style="fixed-case">CTL</jats:styled-content>2 de novo synthesis was not induced after priming with <jats:styled-content style="fixed-case">LPS</jats:styled-content>, indicating that increased <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibody binding was likely caused by translocation of intracellular <jats:styled-content style="fixed-case">CTL</jats:styled-content>2 to the surface or by increased affinity of <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibodies to <jats:styled-content style="fixed-case">CTL</jats:styled-content>2. <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibodies influenced <jats:styled-content style="fixed-case">CD</jats:styled-content>11b surface expression on neutrophils only marginally, which was also not potentiated by priming with <jats:styled-content style="fixed-case">fMLP</jats:styled-content> or <jats:styled-content style="fixed-case">LPS</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study provides experimental evidence supporting the “threshold model” of <jats:styled-content style="fixed-case">TRALI</jats:styled-content>. Priming of neutrophils with <jats:styled-content style="fixed-case">fMLP</jats:styled-content> or <jats:styled-content style="fixed-case">LPS</jats:styled-content> increases their aggregation response to <jats:styled-content style="fixed-case">HNA</jats:styled-content>‐3a antibodies by lowering the required antibody amount.</jats:p></jats:sec>