Possible involvement of heparin-binding protein in transfusion-related acute lung injury.
BACKGROUND
In antibody-mediated nonhemolytic transfusion reactions, transfusion-related acute lung injury (TRALI) tends to occur typically within 2 hours after a blood transfusion. White cell 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. The aim of this study was to characterize soluble mediators that are released from cells at an early stage after immune stimulation.


METHODS
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 flow cytometry and by measurement of the release of soluble factors, including perforin, interleukin-6, tumor necrosis factor-alpha, and heparin-binding protein (HBP) with enzyme-linked immunosorbent assays. In addition, the involvement of two neutrophil FcgammaRs (FcgammaRIIIb and FcgammaRIIa, also known as CD16 and CD32, respectively) was examined during antibody-induced cell activation with anti-FcgammaR blocking antibodies.


RESULTS
Substantial amounts of HBP were released within 30 minutes of stimulation by human antibodies, although other soluble mediators were not released within the same period. Furthermore, the release of HBP was mediated via signals through both FcgammaRIIIb and FcgammaRIIa.


CONCLUSIONS
HBP appears to be one of the primary effector molecules of antibody-mediated nonhemolytic transfusion reactions including TRALI.
Yasui
Kazuta
K
Japanese Red Cross Osaka Blood Center, Osaka, Japan.
Furuta
Rika A
RA
Matsuyama
Nobuki
N
Fukumori
Yasuo
Y
Kimura
Takafumi
T
Tani
Yoshihiko
Y
Shibata
Hirotoshi
H
Hirayama
Fumiya
F
D000906:Antibodies / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006358:Hot Temperature; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology; D066298:In Vitro Techniques; D009504:Neutrophils / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000276:immunology*; D065227:Transfusion Reaction
C062991:AZU1 protein, human; D000906:Antibodies; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; C428200:FCGR3B protein, human; C080568:Fc gamma receptor IIA; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007155:Immunologic Factors; D017452:Receptors, IgG