title: Interference with TRALI-causing anti-HLA DR alloantibody induction of human pulmonary microvascular endothelial cell injury by purified soluble HLA DR.
abstract: OBJECTIVE
  Antibodies to human leucocyte antigens (HLA) and human polymorphonuclear neutrophil (PMN) antigens are considered etiologic agents of transfusion-related acute lung injury (TRALI). The aim of this study was to clarify the role of anti-HLA DR antibodies in the pathophysiology of TRALI and the ability of purified soluble HLA DR (psHLA DR) to inhibit the release of cytokines in an in vitro model.
  
  
  METHODS
  A coculture of human pulmonary microvascular endothelial cells (HMVEC) and monocytes in the presence of serum containing anti-HLA DR alloantibodies previously associated with cases of TRALI was used as an in vitro TRALI model. The release of leukotriene B(4) (LTB(4)) and tumour necrosis factor-alpha (TNF-alpha), the apoptosis of HMVECs were measured.
  
  
  RESULTS
  The release of LTB(4) and TNF-alpha and apoptosis of HMVECs were observed in the model. The addition of psHLA DR markedly reduced the release of LTB(4) and TNF-alpha and inhibited apoptosis of HMVECs.
  
  
  CONCLUSIONS
  These results support the critical role of anti-HLA DR alloantibodies in the pathogenesis of TRALI and suggest that the soluble HLA DR could inhibit TRALI development caused by anti-HLA DR alloantibodies.
authors.affiliation: Research and Development Department, Central Blood Institute, Japanese Red Cross Society, Tokyo, Japan. m-nishimura@bs.jrc.or.jp
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Satake
authors.forename: H
authors.initials: H
authors.lastname: Okazaki
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
mesh_terms: D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007975:Leukotriene B4 / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D007518:Isoantibodies; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4