title: Donor antibodies to HNA-3a implicated in TRALI reactions prime neutrophils and cause PMN-mediated damage to human pulmonary microvascular endothelial cells in a two-event in vitro model.
abstract: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. Antibodies to HNA-3a are commonly implicated in TRALI. We hypothesized that HNA-3a antibodies prime neutrophils (PMNs) and cause PMN-mediated cytotoxicity through a two-event pathogenesis. Isolated HNA-3a+ or HNA-3a- PMNs were incubated with plasma containing HNA-3a antibodies implicated in TRALI, and their ability to prime the oxidase was measured. Human pulmonary microvascular endothelial cells (HMVECs) were activated with endotoxin or buffer, HNA-3a+ or HNA-3a- PMNs were added, and the coculture was incubated with plasma+/-antibodies to HNA-3a. PMN-mediated damage was measured by counting viable HMVECs/mm2. Plasma containing HNA-3a antibodies primed the fMLP-activated respiratory burst of HNA-3a+, but not HNA-3a-, PMNs and elicited PMN-mediated damage of LPS-activated HMVECs when HNA-3a+, but not HNA-3a-, PMNs were used. Thus, antibodies to HNA-3a primed PMNs and caused PMN-mediated HMVEC cytotoxicity in a two-event model identical to biologic response modifiers implicated in TRALI.
authors.affiliation: Bonfils Blood Center and the Department of Pediatrics, University of Colorado at Denver School of Medicine 80230, USA. christopher.silliman@uchsc.edu
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
authors.forename: Brian R
authors.initials: BR
authors.lastname: Curtis
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Kopko
authors.forename: Samina Y
authors.initials: SY
authors.lastname: Khan
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Kelher
authors.forename: Randy M
authors.initials: RM
authors.lastname: Schuller
authors.forename: Baindu
authors.initials: B
authors.lastname: Sannoh
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ambruso
mesh_terms: D001782:Blood Donors; D002470:Cell Survival; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology; D011652:Pulmonary Circulation; D016897:Respiratory Burst; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology*; D065227:Transfusion Reaction
chemical_list: C518134:HNA-3a antigen, human; D007518:Isoantibodies; D007519:Isoantigens