Interference with TRALI-causing anti-HLA DR alloantibody induction of human pulmonary microvascular endothelial cell injury by purified soluble HLA DR.
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.
Nishimura
M
M
Research and Development Department, Central Blood Institute, Japanese Red Cross Society, Tokyo, Japan. m-nishimura@bs.jrc.or.jp
Hashimoto
S
S
Satake
M
M
Okazaki
H
H
Tadokoro
K
K
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
D006684:HLA-DR Antigens; D007518:Isoantibodies; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4