Possible Involvement of Heparin-Binding Protein in Antibody-Mediated Non-Hemolytic Transfusion Reaction.

In antibody-mediated non-hemolytic transfusion reactions, Transfusion-Related Acute Lung Injury (TRALI) tends to occur immediately after a blood transfusion. Leukocyte antibodies or immune complexes have been frequently shown to be associated with the syndrome, although the mechanisms by which they induce TRALI are poorly understood. To explore the mechanism of TRALI, an in vitro whole blood cell culture assay was established in which cells were stimulated by human antibodies and the activation of neutrophils was monitored by a cell surface marker (Mac-1) with FCM. To identify soluble mediators that were released instantly following immune stimulation, we examined the release of soluble factors, including, Perforin, IL-6, TNF-a, and Heparin binding protein (HBP) using ELISAs. In addition, the involvement of two neutrophil FcγRs (FcγRIIIb and FcγRIIa, also known as CD16 and CD32, respectively) in release of HBP was examined during antibody-induced cell activation using anti-FcγR blocking antibodies. Substantial amounts of HBP were released within 30 min upon stimulation by human antibodies, although other soluble mediators were not released within such an eary period. Furthermore, the release of HBP was mediated via signals though both FcγRIIIb and FcγRIIa. HBP that have been known as a multifunctional molecule in early inflammation appears to be a one of the primary effector molecules of antibody-mediated non-hemolytic transfusion reactions including TRALI.