Does activation of the FcgammaRIIa play a role in the pathogenesis of the acute lung injury/acute respiratory distress syndrome?
Does activation of the FcgammaRIIa play a role in the pathogenesis of the acute lung injury/acute respiratory distress syndrome?
复制标题
DOI：
10.1042/cs20090422
复制
发表时间：
2010-01-26
期刊：
影响因子：
--
通讯作者：
Kurdowska AK
中科院分区：
文献类型：
--
作者：
Fudala R;Krupa A;Stankowska D;Allen TC;Kurdowska AK
急性肺损伤（ALI）及其更严重的急性呼吸窘迫综合征（ARDS）是肺部的炎症性疾病，其特征是低氧血症和弥漫性双侧浸润。上皮完整性破坏和内皮损伤是ALI/ARDS发生的重要因素，肺泡损伤是ALI/ARDS最显著的特征。由此导致的肺微血管通透性的增加促进了炎症细胞向肺泡间隙的涌入。水肿液含有促炎介质和血浆蛋白，包括免疫球蛋白。此外，一些报道描述了ALI/ARDS患者肺液（水肿和支气管肺泡灌洗液）中存在自身抗体和免疫复合物[抗IL-8（白细胞介素-8）自身抗体/IL-8复合物]。这些免疫复合物与急性呼吸窘迫综合征患者肺部的Fcγ IIa受体相关。此外，这些患者肺中fc γ - riia的表达显著升高。FcγRIIa几乎出现在所有髓细胞、血小板和内皮细胞上。它是IgG的低亲和力受体，优先结合聚集的免疫球蛋白和免疫复合物。FcγRs调节吞噬作用和细胞介导的细胞毒性，并启动炎症介质的释放。值得注意的是，在抗中性粒细胞自身抗体与其特异性抗原或抗hla（人白细胞抗原）抗体与靶抗原之间形成的免疫复合物与TRALI（输血相关急性肺损伤）的发病机制有关，重要的是，动物研究表明，FcγRs对这些复合物造成肺损伤至关重要。因此，我们推测FcγRs如FcγRIIa可能参与ALI/ARDS的发病机制。
ALI (acute lung injury) and its more severe form ARDS (acute respiratory distress syndrome) are inflammatory diseases of the lung characterized by hypoxaemia and diffuse bilateral infiltrates. Disruption of epithelial integrity and injury to endothelium are contributing factors of the development of ALI/ARDS, and alveolar damage is the most pronounced feature of ALI/ARDS. The resulting increase in lung microvascular permeability promotes influx of inflammatory cells to the alveolar spaces. Oedema fluid contains pro-nflammatory mediators and plasma proteins, including Igs (immunoglobulins). Moreover, several reports describe the presence of autoantibodies and immune complexes [anti-IL-8 (interleukin-8) autoantibody/IL-8 complexes] in lung fluids (oedema and bronchoalveolar lavage fluids) from patients with ALI/ARDS. These immune complexes associate with FcγRIIa (Fcγ IIa receptor) in lungs of patients with ARDS. Furthermore, the expression of FcγRIIa is substantially elevated in lungs of these patients. FcγRIIa appears on virtually all myeloid cells, platelets and endothelial cells. It is a low-affinity receptor for IgG that preferentially binds aggregated immunoglobulins and immune complexes. FcγRs regulate phagocytosis and cell-mediated cytotoxicity, and initiate the release of inflammatory mediators. It should be noted that immune complexes formed between either anti-neutrophil autoantibodies and their specific antigens or anti-HLA (human leucocyte antigen) antibodies and target antigens are implicated in the pathogenesis of TRALI (transfusion-related acute lung injury), and importantly, animal studies indicate that FcγRs are essential for these complexes to cause damage to the lungs. Therefore, we hypothesize that FcγRs such as FcγRIIa could contribute to the pathogenesis of ALI/ARDS.