Endothelial permeability is increased by the supernatant of peripheral blood mononuclear cells stimulated with HLA Class II antibody

• Published in: Transfusion (Philadelphia, Pa.) Pa.), 2008-10, Vol.48 (10), p.2060-2068
• Main Authors: Wakamoto, Shinobu, Fujihara, Mitsuhiro, Sakagawa, Hisako, Takahashi, Daisuke, Niwa, Koichi, Morioka, Masanobu, Sato, Shinichiro, Kato, Toshiaki, Azuma, Hiroshi, Ikeda, Hisami
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies - immunology; Antibodies - pharmacology; Antigen-Antibody Reactions - immunology; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Capillaries - cytology; Capillaries - immunology; Capillary Permeability - immunology; Cells, Cultured; Endothelial Cells - cytology; Endothelial Cells - immunology; Histocompatibility Antigens Class II - immunology; HLA-DR Antigens - immunology; Humans; Interleukin-1beta - immunology; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Medical sciences; Neutralization Tests; Signal Transduction - immunology; Transfusion Reaction; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumor Necrosis Factor-alpha - immunology; Umbilical Veins - cytology
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/j.1537-2995.2008.01809.x

BACKGROUND: The generation of inflammatory mediators from monocytes activated by HLA Class II antibodies is thought to play important roles in the etiology of nonhemolytic transfusion reactions. Increased permeability of endothelial cells contributes to the pathogenesis of rash, urticaria, angioedema, and pulmonary edema, which are symptoms of transfusion reactions. STUDY DESIGN AND METHODS: We investigated whether inflammatory mediators released from monocytes upon stimulation by HLA Class II antibodies could increase endothelial permeability. Human endothelial cell monolayers were incubated with cell‐free supernatants of peripheral blood mononuclear cells (PBMNCs) stimulated with HLA Class II antibody–containing plasma (anti‐HLA‐DR plasma), which has been implicated in severe nonhemolytic transfusion reactions. The permeability of endothelial cells to dextran was measured. RESULTS: The supernatants of PBMNCs stimulated with the anti‐HLA‐DR plasma in corresponding antigen‐antibody combinations were able to increase endothelial permeability. At least 3 hours of exposure of PBMNCs to anti‐HLA‐DR plasma was required to produce a supernatant that could induce a significant increase in permeability. Simultaneous addition of tumor necrosis factor α (TNF‐α) and interleukin 1β (IL‐1β) neutralizing antibodies to the activated PBMNC supernatant significantly reduced the increase in permeability. Treatment of the endothelial cells with an inhibitor of nuclear factor κB (NF‐κB), but not inhibitors of apoptosis, significantly prevented the increase in permeability. CONCLUSION: Both TNF‐α and IL‐1β, generated from PBMNCs by anti‐HLA‐DR plasma in a corresponding antigen‐antibody–dependent manner, led to an increase in endothelial permeability. The activation of monocytes by the HLA‐DR antibodies and the resultant inflammatory mediators could contribute to the pathogenesis of rash, urticaria, angioedema, and pulmonary edema after transfusion.