Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death.
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.
Benoist
Hervé
H
INSERM U.858 I2MR, Toulouse, France. herve.benoist@inserm.fr
Culerrier
Raphaël
R
Poiroux
Guillaume
G
Ségui
Bruno
B
Jauneau
Alain
A
Van Damme
Els J M
EJ
Peumans
Willy J
WJ
Barre
Annick
A
Rougé
Pierre
P
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D031622:Artocarpus / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D037241:Mannose-Binding Lectins / Q000737:chemistry / Q000494:pharmacology*; D031625:Morus / Q000737:chemistry; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; C090683:artocarpin lectin; C043696:jacalin; C500656:morniga M