Barba L M, Caldwell P R, Downie G H, Camussi G, Brentjens J R, Andres G
J Exp Med. 1983 Dec 1;158(6):2141-58. doi: 10.1084/jem.158.6.2141.
To study the effects of relatively long-term interaction of antibodies with surface antigens of lung endothelium, rabbits were intravenously injected for a maximum of 4 d with goat anti-rabbit lung angiotensin-converting enzyme (Gt anti-RbACE) antibodies. On day 1 69%, on day 2 13%, and on days 3 and 4 of injection none of the rabbits developed lethal pulmonary edema. By immunofluorescence microscopy, deposits of GtIgG, frequently in association with RbC3, were found along the endothelium of alveolar capillary walls in all rabbits studied on day 1, in 57% on day 2, in 33% on day 3, and in none of them on day 4. While in vitro anti-ACE antibodies bound in a linear pattern to the lung endothelium, the binding pattern in vivo was distinctly granular. The in vivo interaction of antibodies with ACE also redistributed ACE in a granular pattern along capillary walls. In contrast to the granular deposition of injected anti-ACE IgG and F(ab')2 fragments of anti-ACE IgG, Fab fragments of anti-ACE IgG localized, without fixing C3, in a linear pattern along the endothelium of lung capillaries and did not modify the normal distribution of ACE. However, when the injection of Fab fragments of Gt anti-RbACE IgG was followed by an injection of Rb anti-GtIgG serum, granular deposits of Gt Fab fragments, RbIgG and RbC3 were seen along alveolar capillary walls. Biochemical measurement of ACE activity in lung homogenates provided data in agreement with those obtained by immunofluorescence microscopy, showing diminished activity to none on day 4, with some return of ACE activity on day 5, 24 h after the last injection of antibody, and normal values on day 21. The results obtained indicate that divalent antibodies to an antigen expressed on the plasma membrane of rabbit lung endothelial cells promotes a rapid redistribution of antigenic receptors, fixation of complement and, in surviving rabbits, disappearance of the antigen from the endothelial cells that are no longer susceptible to immune injury. In vivo "immunologic enzymectomy" induced by a ligand-surface antigen interaction is an example of antigenic modulation. These events may have an important role in the pathogenesis of inflammatory lesions induced by antibodies reacting with antigens expressed on the plasma membrane of cells in the lung and in other organs.
为研究抗体与肺内皮表面抗原的相对长期相互作用的影响，给家兔静脉注射山羊抗家兔肺血管紧张素转换酶（Gt抗RbACE）抗体，最长注射4天。在注射第1天，69%的家兔未发生致死性肺水肿；第2天，13%未发生；在注射第3天和第4天，所有家兔均未发生。通过免疫荧光显微镜检查，在第1天检查的所有家兔中，肺泡毛细血管壁内皮上均发现有GtIgG沉积，常与RbC3相关联；第2天，57%的家兔有沉积；第3天，33%有沉积；第4天，所有家兔均未发现沉积。虽然体外抗ACE抗体以线性方式与肺内皮结合，但体内结合模式明显呈颗粒状。抗体与ACE在体内的相互作用也使ACE沿毛细血管壁呈颗粒状重新分布。与注射的抗ACE IgG及抗ACE IgG的F(ab')2片段的颗粒状沉积不同，抗ACE IgG的Fab片段不固定C3，而是沿肺毛细血管内皮呈线性定位，且未改变ACE的正常分布。然而，当注射Gt抗RbACE IgG的Fab片段后再注射Rb抗GtIgG血清时，沿肺泡毛细血管壁可见Gt Fab片段、RbIgG和RbC3的颗粒状沉积。对肺匀浆中ACE活性的生化测定结果与免疫荧光显微镜检查结果一致，显示第4天活性降低至无活性，在最后一次注射抗体后24小时即第5天，ACE活性有所恢复，第21天恢复至正常值。所得结果表明，针对家兔肺内皮细胞质膜上表达的抗原的二价抗体促进抗原受体的快速重新分布、补体的固定，并且在存活的家兔中，抗原从不再易受免疫损伤的内皮细胞中消失。由配体 - 表面抗原相互作用诱导的体内“免疫酶切除”是抗原调节的一个例子。这些事件可能在抗体与肺及其他器官细胞的质膜上表达的抗原反应所诱导的炎性病变的发病机制中起重要作用。
