Benoist Hervé, Culerrier Raphaël, Poiroux Guillaume, Ségui Bruno, Jauneau Alain, Van Damme Els J M, Peumans Willy J, Barre Annick, Rougé Pierre
INSERM U.858 I2MR, Toulouse, France.
J Leukoc Biol. 2009 Jul;86(1):103-14. doi: 10.1189/jlb.0708434. Epub 2009 Apr 28.
Plant lectins displaying similar single sugar-binding specificity and identical molecular structure might present various biological effects. To explore this possibility, the effects on human lymphocytes of two mannose-specific and structurally closely related lectins, Morniga M from Morus nigra and artocarpin from Artocarpus integrifolia were investigated. In silico analysis revealed that Morniga M presents a more largely open carbohydrate-binding cavity than artocarpin, probably allowing interactions with a broader spectrum of carbohydrate moieties. In vitro, Morniga M interacted strongly with the lymphocyte surface and was uptaken quickly by cells. Morniga M and artocarpin triggered the proliferation and activation of human T and NK lymphocytes. A minority of B lymphocytes was activated in artocarpin-treated culture, whereas Morniga M favored the emergence of CD4+ CD8+ T lymphocytes. Moreover, cell death occurred in activated PBMC, activated T lymphocytes, and Jurkat T leukemia cells incubated with Morniga M only. The biological effects of both lectins were dependent on carbohydrate recognition. The Morniga M-induced cell death resulted, at least in part, from caspase-dependent apoptosis and FADD-dependent receptor-mediated cell death. Finally, Morniga M, but not artocarpin, triggered AICD of T lymphocytes. In conclusion, both lectins trigger lymphocyte activation, but only Morniga M induces cell death. In spite of similar in vitro mannose-binding specificities and virtually identical structure, only Morniga M probably interacts with carbohydrate moieties bound to molecules able to induce cell death. The present data suggest that subtle alterations in N-glycans can distinguish activation and cell death molecules at the lymphocyte surface.
具有相似单糖结合特异性和相同分子结构的植物凝集素可能呈现出多种生物学效应。为探究这种可能性，研究了两种对甘露糖具有特异性且结构密切相关的凝集素，即来自黑桑的Morniga M和来自波罗蜜的面包果凝集素对人淋巴细胞的影响。计算机模拟分析表明，Morniga M的碳水化合物结合腔比面包果凝集素更开放，可能允许与更广泛的碳水化合物部分相互作用。在体外，Morniga M与淋巴细胞表面强烈相互作用，并迅速被细胞摄取。Morniga M和面包果凝集素均可触发人T淋巴细胞和NK淋巴细胞的增殖与活化。在面包果凝集素处理的培养物中，少数B淋巴细胞被激活，而Morniga M更有利于CD4+CD8+T淋巴细胞的出现。此外，仅在与Morniga M孵育的活化外周血单核细胞、活化T淋巴细胞和Jurkat T白血病细胞中发生细胞死亡。两种凝集素的生物学效应均依赖于碳水化合物识别。Morniga M诱导的细胞死亡至少部分是由半胱天冬酶依赖性凋亡和FADD依赖性受体介导的细胞死亡所致。最后，Morniga M而非面包果凝集素触发了T淋巴细胞的活化诱导细胞死亡。总之，两种凝集素均触发淋巴细胞活化，但只有Morniga M诱导细胞死亡。尽管在体外具有相似的甘露糖结合特异性且结构几乎相同，但只有Morniga M可能与结合在能够诱导细胞死亡的分子上的碳水化合物部分相互作用。目前的数据表明，N-聚糖的细微改变可以区分淋巴细胞表面的活化分子和细胞死亡分子。
