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

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/mm(2). 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. (Blood. 2007; 109:1752-1755) (c) 2007 by The American Society of Hematology.