輸血関連急性肺障害に関与した抗HLA Class II抗体陽性血漿と末梢血単核細胞及び血管内皮細胞の共培養による内皮細胞の透過性亢進
【背景】輸血関連急性肺障害（transfusion-related acute lung injury：TRALI）の病因に，抗HLA Class II抗体による標的抗原陽性単球の活性化が関与していると考えられる．また，TRALIの特徴的な症状である肺水腫は血管透過性の亢進により誘導される． 【方法】TRALIにおける肺水腫の形成に抗HLA Class II抗体と単球が関与する可能性を調べるため，TRALIの原因製剤となった抗HLA Class II抗体陽性血漿（抗HLA-DR血漿）存在下で，ヒト末梢血単核細胞（peripheral blood mononuclear cell：PBMNC）と...
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| Published in | 日本輸血細胞治療学会誌 Vol. 57; no. 6; pp. 490 - 499 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本輸血・細胞治療学会
2011
日本輸血・細胞治療学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1881-3011 1883-0625 |
| DOI | 10.3925/jjtc.57.490 |
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| Abstract | 【背景】輸血関連急性肺障害（transfusion-related acute lung injury：TRALI）の病因に，抗HLA Class II抗体による標的抗原陽性単球の活性化が関与していると考えられる．また，TRALIの特徴的な症状である肺水腫は血管透過性の亢進により誘導される． 【方法】TRALIにおける肺水腫の形成に抗HLA Class II抗体と単球が関与する可能性を調べるため，TRALIの原因製剤となった抗HLA Class II抗体陽性血漿（抗HLA-DR血漿）存在下で，ヒト末梢血単核細胞（peripheral blood mononuclear cell：PBMNC）とヒト肺微小血管内皮細胞（human lung microvascular endothelial cells：HMVEC）を共培養し，血管透過性亢進の有無を調べた．同様の実験を正常ヒト臍帯静脈内皮細胞（human umbilical vein endothelial cells：HUVEC）を用いて行った．血管透過性は，共培養に添加した蛍光標識デキストランの透過性を測定することにより評価した． 【結果】抗HLA-DR血漿存在下でPBMNCsとHMVECsまたはHUVECsを共培養することにより，血管内皮細胞の透過性が亢進した．この作用は抗体の特異性に依存していた．共培養にplatelet activating factor（PAF）のアンタゴニストであるCV-3988を添加することにより，血管透過性亢進作用はほぼ完全に抑制された．抗TNF-α中和抗体単独及び同抗体と抗IL-1β中和抗体の両方を共培養に添加することにより，HMVECsとHUVECの透過性亢進作用はそれぞれ部分的に抑制された． 【考察】抗HLA Class II抗体の存在下で標的抗原を発現する単球と血管内皮細胞を共培養することにより，血管透過性亢進が誘導された．この反応にPAF，TNF-αまたはIL-1βが関与していると考えられた．従って，抗HLA Class II抗体による単球の活性化は，TRALIにおける肺水腫の病態形成に関与することが示唆された． |
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| AbstractList | 【背景】輸血関連急性肺障害(transfusion-related acute lung injury : TRALI)の病因に, 抗HLA Class II抗体による標的抗原陽性単球の活性化が関与していると考えられる. また, TRALIの特徴的な症状である肺水腫は血管透過性の亢進により誘導される. 【方法】TRALIにおける肺水腫の形成に抗HLA Class II抗体と単球が関与する可能性を調べるため, TRALIの原因製剤となった抗HLA Class II抗体陽性血漿(抗HLA-DR血漿)存在下で, ヒト末梢血単核細胞(peripheral blood mononuclear cell : PBMNC)とヒト肺微小血管内皮細胞(human lung microvascular endothelial cells : HMVEC)を共培養し, 血管透過性亢進の有無を調べた. 同様の実験を正常ヒト臍帯静脈内皮細胞(human umbilical vein endothelial cells : HUVEC)を用いて行った. 血管透過性は, 共培養に添加した蛍光標識デキストランの透過性を測定することにより評価した. 【結果】抗HLA-DR血漿存在下でPBMNCsとHMVECsまたはHUVECsを共培養することにより, 血管内皮細胞の透過性が亢進した. この作用は抗体の特異性に依存していた. 共培養にplatelet activating factor (PAF)のアンタゴニストであるCV-3988を添加することにより, 血管透過性亢進作用はほぼ完全に抑制された. 抗TNF-α中和抗体単独及び同抗体と抗IL-1β中和抗体の両方を共培養に添加することにより, HMVECsとHUVECの透過性亢進作用はそれぞれ部分的に抑制された. 【考察】抗HLA Class II抗体の存在下で標的抗原を発現する単球と血管内皮細胞を共培養することにより, 血管透過性亢進が誘導された. この反応にPAF, TNF-αまたはIL-1βが関与していると考えられた. 従って, 抗HLA Class II抗体による単球の活性化は, TRALIにおける肺水腫の病態形成に関与することが示唆された. 【背景】輸血関連急性肺障害（transfusion-related acute lung injury：TRALI）の病因に，抗HLA Class II抗体による標的抗原陽性単球の活性化が関与していると考えられる．また，TRALIの特徴的な症状である肺水腫は血管透過性の亢進により誘導される． 【方法】TRALIにおける肺水腫の形成に抗HLA Class II抗体と単球が関与する可能性を調べるため，TRALIの原因製剤となった抗HLA Class II抗体陽性血漿（抗HLA-DR血漿）存在下で，ヒト末梢血単核細胞（peripheral blood mononuclear cell：PBMNC）とヒト肺微小血管内皮細胞（human lung microvascular endothelial cells：HMVEC）を共培養し，血管透過性亢進の有無を調べた．同様の実験を正常ヒト臍帯静脈内皮細胞（human umbilical vein endothelial cells：HUVEC）を用いて行った．血管透過性は，共培養に添加した蛍光標識デキストランの透過性を測定することにより評価した． 【結果】抗HLA-DR血漿存在下でPBMNCsとHMVECsまたはHUVECsを共培養することにより，血管内皮細胞の透過性が亢進した．この作用は抗体の特異性に依存していた．共培養にplatelet activating factor（PAF）のアンタゴニストであるCV-3988を添加することにより，血管透過性亢進作用はほぼ完全に抑制された．抗TNF-α中和抗体単独及び同抗体と抗IL-1β中和抗体の両方を共培養に添加することにより，HMVECsとHUVECの透過性亢進作用はそれぞれ部分的に抑制された． 【考察】抗HLA Class II抗体の存在下で標的抗原を発現する単球と血管内皮細胞を共培養することにより，血管透過性亢進が誘導された．この反応にPAF，TNF-αまたはIL-1βが関与していると考えられた．従って，抗HLA Class II抗体による単球の活性化は，TRALIにおける肺水腫の病態形成に関与することが示唆された． |
| Author | 東, 寛 佐藤, 進一郎 池田, 久實 若本, 志乃舞 藤原, 満博 高橋, 大輔 加藤, 俊明 丹羽, 光一 |
| Author_FL | NIWA Koichi IKEDA Hisami TAKAHASHI Daisuke SATO Shinichiro FUJIHARA Mitsuhiro WAKAMOTO Shinobu KATO Toshiaki AZUMA Hiroshi |
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Vox Sang, 41: 25-31, 1981. 13) Fujihara M, Wakamoto S, Azuma H, et al: Involvement of human leukocyte antigen Class II antibody in pathogenesis of transfusion-related acute lung injury (TRALI) : vascular permeability enhancement. Vascular Disease Prevention, 6: 170-177, 2009. 38) Imaizumi TA, Stafforini DM, Yamada Y, et al: Platelet-activating factor: a mediator for clinicians. J Intern Med, 238: 5-20, 1995. 9) Kopko PM, Paglieroni TG, Popovsky MA, et al: TRALI: correlation of antigen-antibody and monocyte activation in donor-recipient pairs. Transfusion, 43: 177-184, 2003. 18) Nishimura M, Mitsunaga S, Juji T: Frozen-stored granulocytes can be used for an immunofluorescence test to detect granulocyte antibodies. Transfusion, 41: 1268-1272, 2001. 22) Bossi F, Fischetti F, Pellis V, et al: Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. 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Transfusion, 40: 861-866, 2000. 12) Sakagawa H, Miyazaki T, Fujihara M, et al: Generation of inflammatory cytokines and chemokines from peripheral blood mononuclear cells by HLA Class II antibody-containing plasma unit that was associated with severe nonhemolytic transfusion reactions. Transfusion, 47: 154-161, 2007. 14) Wakamoto S, Fujihara M, Sakagawa H, et al: Endothelial permeability is increased by the supernatant of peripheral blood mononuclear cells stimulated with HLA Class II antibody. Transfusion, 48: 2060-2068, 2008. 8) Nicolle AL, Chapman CE, Carter V, et al: Transfusion-related acute lung injury caused by two donors with anti-human leucocyte antigen Class II antibodies: a look-back investigation. Transfus Med, 14: 225-230, 2004. 24) Sjöström M, Johansson AS, Schröder O, et al: Dominant expression of the CysLT2 receptor accounts for calcium signaling by cysteinyl leukotrienes in human umbilical vein endothelial cells. Arterioscler Thromb Vasc Biol, 23: e37-41, 2003. 28) Valone FH, Epstein LB: Biphasic platelet-activating factor synthesis by human monocytes stimulated with IL-1β, tumor necrosis factor, or IFN-γ. J Immunol, 141: 3945-3950, 1988. 30) Clavijo LC, Carter MB, Matheson PJ, et al: PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat. J Appl Physiol, 90: 261-268, 2001. 37) Venable ME, Zimmerman GA, McIntyre TM, et al: Platelet-activating factor: a phospholipid autacoid with diverse actions. J Lipid Res, 34: 691-702, 1993. 26) Montrucchio G, Alloatti G, Camussi G: Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev, 80: 1669-1699, 2000. |
| References_xml | – reference: 11) Nishimura M, Hashimoto S, Satake M, et al: Interference with TRALI-causing anti-HLA DR alloantibody induction of human pulmonary microvascular endothelial cell injury by purified soluble HLA DR. Vox Sang, 93: 78-82, 2007. – reference: 16) Moses LA, Stroncek DF, Cipolone KM, et al: Detection of HLA antibodies by using flow cytometry and latex beads coated with HLA antigens. Transfusion, 40: 861-866, 2000. – reference: 9) Kopko PM, Paglieroni TG, Popovsky MA, et al: TRALI: correlation of antigen-antibody and monocyte activation in donor-recipient pairs. Transfusion, 43: 177-184, 2003. – reference: 18) Nishimura M, Mitsunaga S, Juji T: Frozen-stored granulocytes can be used for an immunofluorescence test to detect granulocyte antibodies. Transfusion, 41: 1268-1272, 2001. – reference: 22) Bossi F, Fischetti F, Pellis V, et al: Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. J Immunol, 173: 6921-6927, 2004. – reference: 32) Sisson JH, Prescott SM, McIntyre TM, et al: Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes. Correlation of synthesis with release, functional events, and leukotriene B4 metabolism. J Immunol, 138: 3918-3926, 1987. – reference: 13) Fujihara M, Wakamoto S, Azuma H, et al: Involvement of human leukocyte antigen Class II antibody in pathogenesis of transfusion-related acute lung injury (TRALI) : vascular permeability enhancement. Vascular Disease Prevention, 6: 170-177, 2009. – reference: 1) Kleinman S, Caulfield T, Chan P, et al: Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion, 44: 1774-1789, 2004. – reference: 36) Poubelle PE, Gingras D, Demers C, et al: Platelet-activating factor (PAF-acether) enhances the concomitant production of tumor necrosis factor-alpha and interleukin-1 by subsets of human monocytes. Immunology, 72: 181-187, 1991. – reference: 39) Bhatia M, Moochhala S: Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol, 202: 145-156, 2004. – reference: 31) Chang SW, Feddersen CO, Henson PM, et al: Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats. J Clin Invest, 79: 1498-1509, 1987. – reference: 15) Shigematsu A, Yonezumi M, Imai K, et al: Transfusion-related acute lung injury caused by anti-HLA antibody in a patient with myelodysplasitic syndrome and gastric cancer. J Jpn Transfus Med, 50: 720-725, 2004. – reference: 10) Nishimura M, Hashimoto S, Takanashi M, et al: Role of anti-human leucocyte antigen Class II alloantibody and monocytes in development of transfusion-related acute lung injury. Transfus Med, 17: 129-134, 2007. – reference: 17) Shibata Y, Juji T, Nishizawa Y, et al: Detection of platelet antibodies by a newly developed mixed agglutination with platelets. Vox Sang, 41: 25-31, 1981. – reference: 7) Wallis JP, Lubenko A, Wells AW, et al: Single hospital experience of TRALI. Transfusion, 43: 1053-1059, 2003. – reference: 12) Sakagawa H, Miyazaki T, Fujihara M, et al: Generation of inflammatory cytokines and chemokines from peripheral blood mononuclear cells by HLA Class II antibody-containing plasma unit that was associated with severe nonhemolytic transfusion reactions. Transfusion, 47: 154-161, 2007. – reference: 2) Bux J, Sachs UH: The pathogenesis of transfusion-related acute lung injury (TRALI). 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| Snippet | 【背景】輸血関連急性肺障害（transfusion-related acute lung injury：TRALI）の病因に，抗HLA Class II抗体による標的抗原陽性単球の活性化が関与していると考えられる．また，TRALIの特徴的な症状である肺水腫は血管透過性の亢進により誘導される．... 【背景】輸血関連急性肺障害(transfusion-related acute lung injury : TRALI)の病因に, 抗HLA Class II抗体による標的抗原陽性単球の活性化が関与していると考えられる. また, TRALIの特徴的な症状である肺水腫は血管透過性の亢進により誘導される.... |
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| SubjectTerms | HLA Class II antibody increase in endothelial cell permeability monocyte activation TRALI ヒト末梢血単核細胞の活性化 抗 HLA Class II 抗体 抗HLA Class II抗体 血管内皮細胞の透過性亢進 |
| Title | 輸血関連急性肺障害に関与した抗HLA Class II抗体陽性血漿と末梢血単核細胞及び血管内皮細胞の共培養による内皮細胞の透過性亢進 |
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| ispartofPNX | 日本輸血細胞治療学会誌, 2011, Vol.57(6), pp.490-499 |
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