Hokkaido Red Cross Blood Center, Sapporo, Japan.
Transfusion. 2011 May;51(5):993-1001. doi: 10.1111/j.1537-2995.2010.02910.x. Epub 2010 Oct 26.
HLA Class II antibody-initiated activation of monocytes possessing the corresponding antigen is thought to participate in the pathogenesis of transfusion-related acute lung injury (TRALI). Pulmonary edema, a hallmark of TRALI, is caused by increasing vascular permeability.
To investigate the contribution of HLA Class II antibody and monocytes to the development of pulmonary edema in TRALI, we studied whether the permeability of human lung microvascular endothelial cells (HMVECs) could be enhanced by coculturing HMVECs with peripheral blood mononuclear cells (PBMNCs) in the presence of HLA Class II antibody-containing plasma, which was implicated in TRALI (anti-HLA-DR plasma). In addition, similar experiments were performed with human umbilical vein endothelial cells (HUVECs). The endothelial permeability to fluoresceinated dextran, which was added from the start of coculture, was measured.
The coculture of HMVECs or HUVECs with PBMNCs in the presence of anti-HLA-DR plasma resulted in the increase of endothelial permeability in the corresponding antigen-antibody-dependent manner. CV-3988, a platelet-activating factor (PAF) receptor antagonist, almost completely suppressed the increase in endothelial permeability. Neutralizing antibodies to tumor necrosis factor (TNF)-α alone and simultaneous addition of the antibodies to TNF-α and interleukin (IL)-1β to the coculture partially suppressed the permeability increase of HMVECs and HUVECs, respectively.
HLA Class II antibody and monocytes in the corresponding antigen-antibody combination caused the enhancement of endothelial permeability. PAF, TNF-α, and/or IL-1β might be involved in the endothelial permeability increase. HLA Class II antibody-initiated monocyte activation could lead to the development of pulmonary edema in TRALI.
HLA II 类抗体激活具有相应抗原的单核细胞被认为参与了输血相关性急性肺损伤（TRALI）的发病机制。肺水肿是 TRALI 的标志，是由血管通透性增加引起的。
为了研究 HLA II 类抗体和单核细胞对 TRALI 中肺水肿发展的贡献，我们研究了在含有 HLA II 类抗体的血浆（与 TRALI 相关的抗 HLA-DR 血浆）存在的情况下，单核细胞与外周血单核细胞（PBMNC）共培养是否会增强人肺微血管内皮细胞（HMVEC）的通透性。此外，还用人脐静脉内皮细胞（HUVEC）进行了类似的实验。从共培养开始就加入荧光标记的葡聚糖，测量内皮通透性的变化。
在抗 HLA-DR 血浆存在的情况下，HMVEC 或 HUVEC 与 PBMNC 的共培养导致内皮通透性以相应的抗原抗体依赖的方式增加。血小板激活因子（PAF）受体拮抗剂 CV-3988 几乎完全抑制了内皮通透性的增加。单独使用肿瘤坏死因子（TNF）-α的中和抗体，以及同时将 TNF-α和白细胞介素（IL）-1β的抗体添加到共培养中，分别部分抑制了 HMVEC 和 HUVEC 的通透性增加。
相应抗原抗体组合中的 HLA II 类抗体和单核细胞导致内皮通透性增强。PAF、TNF-α和/或 IL-1β可能参与了内皮通透性的增加。HLA II 类抗体激活的单核细胞活化可能导致 TRALI 中肺水肿的发生。
