Antibody-induced neutrophil activation as a trigger for transfusion-related acute lung injury in an ex vivo rat lung model.
Transfusion-related acute lung injury (TRALI) is a hazardous complication of transfusion and has become the leading cause of transfusion-related death in the United States and United Kingdom. Although leukoagglutinating antibodies have been frequently shown to be associated with the syndrome, the mechanism by which they induce TRALI is poorly understood. Therefore, we reproduced TRALI in an ex vivo rat lung model. Our data demonstrate that TRALI induction by antileukocyte antibodies is dependent on the density of the cognate antigen but does not necessarily require leukoagglutinating properties of the antibody or the presence of complement proteins. Rather, antibody-mediated activation of neutrophils seems to initiate TRALI, a process that could be triggered by neutrophil stimulation with fMLP. Antibody-mediated neutrophil activation and subsequent release of reactive oxygen species may thus represent key events in the pathophysiologic cascade that leads to immune TRALI.
Sachs
Ulrich J H
UJ
Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University Giessen, Germany. ulrich.sachs@med.uni-giessen.de
Hattar
Katja
K
Weissmann
Norbert
N
Bohle
Rainer M
RM
Weiss
Timo
T
Sibelius
Ulf
U
Bux
Juergen
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001803:Blood Transfusion; D004195:Disease Models, Animal; D006098:Granulocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D055370:Lung Injury; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017382:Reactive Oxygen Species / Q000276:immunology; D065227:Transfusion Reaction
D000911:Antibodies, Monoclonal; D007519:Isoantigens; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine