Probing the cons and pros of lectin-induced immunomodulation: case studies for the mistletoe lectin and galectin-1.
When imagining to monitor animal cells through a microscope with resolution at the molecular level, a salient attribute of their surfaces will be the abundance of glycan chains. They present galactosides at their termini widely extending like tentacles into the extracellular space. Their spatial accessibility and their potential for structural variability endow especially these glycan parts with capacity to act as docking points for molecular sensors (sugar receptors such as lectins). Binding and ligand clustering account for transmission of post-binding signals into the cell interior. The range of triggered activities has turned plant lectins into popular tools in cell biology and immunology. Potential for clinical application has been investigated rigorously only in recent years. As documented in vitro and in vivo for the galactoside-specific mistletoe lectin, its apparent immunomodulatory capacity reflected in upregulation of production of proinflammatory cytokines will not necessarily be clinically favorable but a double-edged sword. In fact, lectin application has been shown to stimulate tumor growth in cell lines, histocultures of human tumors and in two animal models using chemical carcinogenesis or tumor transplantation. When testing immunological effects of the endogenous lectin galectin-1, protection against disorders mediated by activated T cells came up for consideration. Elimination of these cells via CD7-dependent induction of apoptosis, and a shift to the Th2 response by the galectin, are factors to ameliorate disease states. This result encourages further efforts with other galectins. Functional redundancy, synergism, diversity or antagonism among galectins are being explored to understand the actual role of this class of endogenous lectins in inflammation. Regardless of the results of further preclinical testing for galectin-1, these two case studies break new ground in our understanding how glycans as ligands for lectins convey reactivity to immune cells, with impact on the course of a tumor or autoimmune disease.
Gabius
H J
HJ
Lehrstuhl für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, 80539 Munich, Germany. gabius@tiph.vetmed.uni-muenchen.de
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005697:Galactosides / Q000276:immunology; D037483:Galectin 1; D006388:Hemagglutinins / Q000494:pharmacology; D006801:Humans; D037102:Lectins / Q000493:pharmacokinetics / Q000494:pharmacology*; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D014784:Mistletoe / Q000737:chemistry*; D037121:Plant Lectins; D012509:Sarcoma / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D016207:Cytokines; D005697:Galactosides; D037483:Galectin 1; D006388:Hemagglutinins; D037102:Lectins; D037121:Plant Lectins