title: Antibodies to the HLA-A2 antigen prime neutrophils and serve as the second event in an in vitro model of transfusion-related acute lung injury.
abstract: BACKGROUND
  Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality and has been linked to the infusion of donor antibodies directed against recipient HLA class I antigens. We hypothesize that antibodies against HLA class I antigens bind to the antigens on the neutrophil (PMN) surface and induce priming and PMN cytotoxicity as the second event in a two-event in vitro model of PMN-mediated cytotoxicity.
  
  
  METHODS
  Isolated PMNs from HLA-A2 homozygotes, heterozygotes and null donors were incubated with a monoclonal antibody to HLA-A2 and a human polyclonal IgG to HLA-A2 and priming of the oxidase was measured. The monoclonal antibodies and PMNs from these three groups were then used in a two-event model of PMN cytotoxicity.
  
  
  RESULTS
  The antibodies to HLA-A2 both primed PMNs from HLA-A2 homozygotes but not from heterozygotes or nulls. Antibodies to HLA-A2 also served as the second event in a two-event model to induce PMN cytotoxicity of HLA-A2 homozygous PMNs.
  
  
  CONCLUSIONS
  Antibodies to HLA class I antigens may directly prime/activate PMNs through the ligation of the antigen on the cell surface, and the antigen density appears to be important for these changes in PMN physiology.
authors.affiliation: The Research Laboratory, Bonfils Blood Center, Denver, CO, USA; Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO, USA; Department of Surgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
authors.forename: R S
authors.initials: RS
authors.lastname: Bercovitz
authors.forename: S Y
authors.initials: SY
authors.lastname: Khan
authors.forename: M R
authors.initials: MR
authors.lastname: Kelher
authors.forename: M
authors.initials: M
authors.lastname: LaSarre
authors.forename: K J
authors.initials: KJ
authors.lastname: Land
authors.forename: S
authors.initials: S
authors.lastname: Sowemimo-Coker
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology*; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology*; D065227:Transfusion Reaction
chemical_list: D000911:Antibodies, Monoclonal; D015789:HLA-A2 Antigen
keywords: cytotoxicity; homozygous HLA-A2; pulmonary endothelium