Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.
Toxins (Basel). 2022 Sep 2;14(9):614. doi: 10.3390/toxins14090614.
Abrin is a highly toxic protein obtained from the seeds of the rosary pea plant , and it is closely related to ricin in terms of its structure and chemical properties. Both toxins inhibit ribosomal function, halt protein synthesis and lead to cellular death. The major clinical manifestations following pulmonary exposure to these toxins consist of severe lung inflammation and consequent respiratory insufficiency. Despite the high similarity between abrin and ricin in terms of disease progression, the ability to protect mice against these toxins by postexposure antibody-mediated treatment differs significantly, with a markedly higher level of protection achieved against abrin intoxication. In this study, we conducted an in-depth comparison between the kinetics of in vivo abrin and ricin intoxication in a murine model. The data demonstrated differential binding of abrin and ricin to the parenchymal cells of the lungs. Accordingly, toxin-mediated injury to the nonhematopoietic compartment was shown to be markedly lower in the case of abrin intoxication. Thus, profiling of alveolar epithelial cells demonstrated that although toxin-induced damage was restricted to alveolar epithelial type II cells following abrin intoxication, as previously reported for ricin, it was less pronounced. Furthermore, unlike following ricin intoxication, no direct damage was detected in the lung endothelial cell population following abrin exposure. Reduced impairment of intercellular junction molecules following abrin intoxication was detected as well. In contrast, similar damage to the endothelial surface glycocalyx layer was observed for the two toxins. We assume that the reduced damage to the lung stroma, which maintains a higher level of tissue integrity following pulmonary exposure to abrin compared to ricin, contributes to the high efficiency of the anti-abrin antibody treatment at late time points after exposure.
相思豆毒素是从罗勒豌豆植物的种子中提取的一种高毒性蛋白，其结构和化学性质与蓖麻毒素密切相关。这两种毒素均能抑制核糖体的功能，阻止蛋白质合成，导致细胞死亡。这些毒素经肺部暴露后的主要临床表现为严重的肺部炎症和随后的呼吸功能不全。尽管相思豆毒素和蓖麻毒素在疾病进展方面具有高度相似性，但通过暴露后抗体介导的治疗来保护小鼠免受这些毒素的能力存在显著差异，对相思豆毒素中毒的保护水平明显更高。在这项研究中，我们在小鼠模型中对相思豆毒素和蓖麻毒素体内中毒的动力学进行了深入比较。数据表明，相思豆毒素和蓖麻毒素与肺部实质细胞的结合存在差异。因此，与相思豆毒素中毒相比，毒素介导的非造血细胞损伤明显较低。因此，对肺泡上皮细胞的分析表明，尽管相思豆毒素中毒后，如先前报道的蓖麻毒素那样，仅限于肺泡上皮 II 型细胞，但毒素诱导的损伤程度较轻。此外，与蓖麻毒素中毒不同，相思豆暴露后未检测到肺内皮细胞群中存在直接损伤。还检测到相思豆毒素中毒后细胞间连接分子的损伤减少。相比之下，两种毒素对内皮表面糖萼层的损伤相似。我们假设，与蓖麻毒素相比，相思豆毒素对肺基质的损伤较小，这有助于在暴露后晚期使用抗相思豆毒素抗体进行治疗的高效性。
