Impact of priming on the response of neutrophils to human neutrophil alloantigen‐3a antibodies

Abstract

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.

Human neutrophil antigen‐3a antibodies induce neutrophil stiffening and conformational activation of CD11b without shedding of L‐selectin

“…This is consistent with autopsy findings from fatal HNA‐3a antibody–induced TRALI cases showing congestion of the pulmonary microvasculature with neutrophils including aggregated intravascular neutrophils . These data are also consistent with the threshold model of TRALI . As already mentioned, priming of granulocytes with fMLP or lipopolysaccharide increases the surface expression of CD11b .…”

“…These data are also consistent with the threshold model of TRALI . As already mentioned, priming of granulocytes with fMLP or lipopolysaccharide increases the surface expression of CD11b . HNA‐3a antibodies can then activate more CD11b molecules on neutrophils resulting in increased adhesion and aggregation.…”

Underdiagnosing of antibody‐mediated transfusion‐related acute lung injury: evaluation of cellular‐based versus bead‐based techniques

“…This was also confirmed in a rat model of antibody‐mediated TRALI using MHC‐I antibodies . Recently, the mechanism has also been tested and confirmed for other antibodies involved in antibody‐mediated TRALI such as HNA .…”

HNA antibody‐mediated neutrophil aggregation is dependent on serine protease activity

“…Neutrophils were isolated from ethylenediaminetetraacetic acid (EDTA)‐anticoagulated whole blood of healthy donors by density gradient centrifugation as described and resuspended in RPMI (Biochrom AG, Berlin, Germany) .…”