Published online before print April 28, 2009
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* INSERM U.858 I2MR, Equipe 14, Toulouse, Cedex, France;
IFR31, Institut Louis Bugnard, CHU Rangueil, Toulouse, Cedex, France;
Université Paul Sabatier (Toulouse III), Faculté des Sciences Pharmaceutiques, Services dImmunologie et Biologie Cellulaire, Toulouse, France;
UMR UPS-CNRS 5546, Castanet-Tolosan, France; and
|| Department of Molecular Biotechnology, Laboratory of Biochemistry and Glycobiology, Ghent University, Ghent, Belgium
1. Correspondence: INSERM U.858, Institut Louis Bugnard, CHU de Rangueil, BP 84225, 31432 Toulouse, Cedex 4, France. E-mail: herve.benoist{at}inserm.fr
ABSTRACT
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.
Key Words: Morus nigra Jurkat T cells AICD FADD caspase endocytosis