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Impact of priming on the response of neutrophils to human neutrophil alloantigen‐3a antibodies
Author(s) -
Berthold Tom,
Muschter Stefan,
Schubert Nicole,
Wesche Jan,
Ameling Sabine,
Teumer Alexander,
Reil Angelika,
Bux Jürgen,
Bakchoul Tamam,
Greinacher Andreas
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12898
Subject(s) - priming (agriculture) , granulocyte , immunology , antibody , ctl* , lipopolysaccharide , flow cytometry , neutrophil extracellular traps , medicine , biology , immune system , inflammation , cd8 , botany , germination
Background Human neutrophil alloantigen‐3a ( HNA ‐3a) antibodies can induce transfusion‐related acute lung injury ( TRALI ). The severity of TRALI varies largely among the affected patients. Severe comorbidity seems to increase the susceptibility for TRALI , potentially by priming of neutrophils. Thus, the impact of neutrophil priming on HNA ‐3a antibody–mediated neutrophil aggregation and CD 11b surface expression was investigated. Study Design and Methods Neutrophils were primed using formyl‐methionyl‐leucyl‐phenylalanine ( fMLP ) or bacterial lipopolysaccharide ( LPS ). Granulocyte aggregation and CD 11b surface expression were evaluated by the granulocyte agglutination test and by flow cytometry ( FC ), respectively. Priming‐induced changes in the surface expression of choline transporter‐like protein 2 ( CTL 2) and the CTL 2 m RNA expression were assessed by FC and quantitative real‐time polymerase chain reaction, respectively. Results Priming of neutrophils lowered the amount of HNA ‐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 HNA ‐3a antibodies to neutrophils. However, CTL 2 de novo synthesis was not induced after priming with LPS , indicating that increased HNA ‐3a antibody binding was likely caused by translocation of intracellular CTL 2 to the surface or by increased affinity of HNA ‐3a antibodies to CTL 2. HNA ‐3a antibodies influenced CD 11b surface expression on neutrophils only marginally, which was also not potentiated by priming with fMLP or LPS . Conclusion This study provides experimental evidence supporting the “threshold model” of TRALI . Priming of neutrophils with fMLP or LPS increases their aggregation response to HNA ‐3a antibodies by lowering the required antibody amount.