BACKGROUND AND 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. MATERIALS AND 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. CONCLUSION: 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.
BACKGROUND AND 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. MATERIALS AND 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. CONCLUSION: 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: Nikolaos A Maniatis; Anastasia Kotanidou; John D Catravas; Stylianos E Orfanos Journal: Vascul Pharmacol Date: 2008-07-29 Impact factor: 5.773