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. Blood 2007 Feb 15;109(4):1752-5
Date
10/14/2006Pubmed ID
17038531Pubmed Central ID
PMC1794055DOI
10.1182/blood-2006-05-025106Scopus ID
2-s2.0-33846914829 (requires institutional sign-in at Scopus site) 106 CitationsAbstract
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.
Author List
Silliman CC, Curtis BR, Kopko PM, Khan SY, Kelher MR, Schuller RM, Sannoh B, Ambruso DRAuthor
Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
Blood DonorsCell Survival
Coculture Techniques
Cytotoxicity, Immunologic
Endothelial Cells
Endothelium, Vascular
Humans
Isoantibodies
Isoantigens
Neutrophil Activation
Neutrophils
Pulmonary Circulation
Respiratory Burst
Transfusion Reaction
