Submitted May 24, 2006
Accepted September 28, 2006
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
Christopher C Silliman*, Brian R Curtis, Patricia M Kopko, Samina Y Khan, Marguerite R Kelher, Randy M Schuller, Baindu Sannoh, and Daniel R Ambruso
Bonfils Blood Center & Departments of Pediatrics and Surgery, University of Colorado at Denver School of Medicine, Denver, CO
Blood Center of Southeastern Wisconsin, Milwaukee, WI
BloodSource, Sacramento, CA
Department of Pediatrics, University of Colorado at Denver School of Medicine, Denver, CO
Department of Surgery, Univeristy of Colorado at Denver School of Medicine, Denver, CO
American Red Cross - North Central Blood Services, St. Paul, MN
Bonfils Blood Center and Department of Pediatrics, University of Colorado at Denver School of Medicine, Denver, CO
* Corresponding author; email: christopher.silliman{at}uchsc.edu.
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 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 - PMNs were added, and the co-culture 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.
