BINDING OF MONOCLONAL-ANTIBODY AA4 TO GANGLIOSIDES ON RAT BASOPHILIC LEUKEMIA-CELLS PRODUCES CHANGES SIMILAR TO THOSE SEEN WITH FC-EPSILON RECEPTOR ACTIVATION
BINDING OF MONOCLONAL-ANTIBODY AA4 TO GANGLIOSIDES ON RAT BASOPHILIC LEUKEMIA-CELLS PRODUCES CHANGES SIMILAR TO THOSE SEEN WITH FC-EPSILON RECEPTOR ACTIVATION
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DOI：
10.1083/jcb.116.3.635
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发表时间：
1992-02-01
影响因子：
7.8
通讯作者：
SIRAGANIAN, RP
中科院分区：
文献类型：
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作者：
OLIVER, C;SAHARA, N;SIRAGANIAN, RP
mAb AA4 与神经节苷脂 G(D1b) 大鼠嗜碱性白血病 (RBL-2H3) 细胞的新型衍生物结合。一些神经节苷脂位于高亲和力 IgE 受体 (Fc-epsilon-RI) 附近，mAb AA4 的结合会抑制 Fc-epsilon-RI 介导的组胺释放。在本研究中，发现 mAb AA4 只与所有受检大鼠组织中的肥大细胞结合。在体外，mAb AA4 结合后 1 分钟内，细胞经历了惊人的形态变化。它们失去了正常的纺锤形外观，增加了褶皱，并散布在培养皿的表面上。这些变化伴随着细胞骨架元素、肌动蛋白、微管蛋白和波形蛋白的重新分布，但只有肌动蛋白与膜褶皱相关。 mAb AA4 的结合还会诱导细胞内钙的升高，刺激磷脂酰肌醇分解并激活 PKC。然而，这些变化的程度小于用针对 Fc-ε-RI 的抗原或抗体刺激细胞时观察到的变化程度。当细胞暴露于非特异性 IgG、IgE 或四种其他抗细胞表面抗体时，没有观察到与 mAb AA4 结合相关的这些变化，也没有观察到在 4 摄氏度或缺乏细胞外钙的情况下结合 mAb AA4 引起的变化。尽管 mAb AA4 不会刺激组胺释放，但它会增强钙离子载体 A23187 介导的释放的效果。 mAb AA4 产生的形态和生化效应与通过 IgE 受体激活细胞后所观察到的相似。因此，结合 mAb AA4 的表面神经节苷脂可能在调节分泌事件中发挥作用。
The mAb AA4 binds to novel derivatives of the ganglioside G(D1b) rat basophilic leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high affinity IgE receptor (Fc-epsilon-RI), and binding of mAb AA4 inhibits Fc-epsilon-RI-mediated histamine release. In the present study, mAb AA4 was found to bind exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of mAb AA4 binding, the cells underwent striking morphologic changes. They lost their normal spindle shaped appearance, increased their ruffling, and spread over the surface of the culture dish. These changes were accompanied by a redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but only the actin was associated with the membrane ruffles. Binding of mAb AA4 also induces a rise in intracellular calcium, stimulates phosphatidyl inositol breakdown, and activates PKC. However, the extent of these changes was less than that observed when the cells were stimulated with antigen or antibody directed against the Fc-epsilon-RI. None of these changes associated with mAb AA4 binding were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti-cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4-degrees-C or in the absence of extracellular calcium. Although mAb AA4 does not stimulate histamine release, it enhances the effect of the calcium ionophore A23187 mediated release. The morphological and biochemical effects produced by mAb AA4 are similar to those seen following activation of the cell through the IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function in modulating secretory events.