Lectin-Based Food Poisoning: A New Mechanism of Protein Toxicity

Abstract

BackgroundIngestion of the lectins present in certain improperly cooked vegetables can result in acute GI tract distress, but the mechanism of toxicity is unknown. In vivo, gut epithelial cells are constantly exposed to mechanical and other stresses and consequently individual cells frequently experience plasma membrane disruptions. Repair of these cell surface disruptions allows the wounded cell to survive: failure results in necrotic cell death. Plasma membrane repair is mediated, in part, by an exocytotic event that adds a patch of internal membrane to the defect site. Lectins are known to inhibit exocytosis. We therefore tested the novel hypothesis that lectin toxicity is due to an inhibitory effect on plasma membrane repair.Methods and FindingsRepair of plasma membrane disruptions and exocytosis of mucus was assessed after treatment of cultured cell models and excised segments of the GI tract with lectins. Plasma membrane disruptions were produced by focal irradiation of individual cells, using a microscope-based laser, or by mechanical abrasion of multiple cells, using a syringe needle. Repair was then assessed by monitoring the cytosolic penetration of dyes incapable of crossing the intact plasma membrane. We found that cell surface-bound lectins potently inhibited plasma membrane repair, and the exocytosis of mucus that normally accompanies the repair response.ConclusionsLectins potently inhibit plasma membrane repair, and hence are toxic to wounded cells. This represents a novel form of protein-based toxicity, one that, we propose, is the basis of plant lectin food poisoning.

Receptor for Advanced Glycation End Products (RAGE) Prevents Endothelial Cell Membrane Resealing and Regulates F-actin Remodeling in a β-Catenin-dependent Manner

“…Impaired Membrane Resealing and Altered F-actin Structures in RAGE-ECV Cells-RAGE, a cell surface glycoprotein, led to the speculation that it may play a role in regulating plasma membrane plasticity because of cell surface glycoproteins are implicated in this event (25). To test this hypothesis, a plasma membrane resealing assay was carried out in ECV-304 and RAGE-ECV cells after laser-induced local membrane injury at the cell periphery.…”

Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens

“…WGA IgG and IgA levels were significantly higher in patients with untreated Celiac disease compared to healthy controls [70]. Although Sollid and colleagues [69] found no cross-reactivity between WGA and gliadin proteins, others have shown that the combination of WGA and gliadin can increase intestinal permeability [71], which leads to an increase of translocating dietary proteins and other antigens into circulation, resulting in inflammation and autoimmunity.…”

“…Lectins and agglutinins are present in a variety of plants, where they serve as defense mechanisms against other plants and fungi. Because of their ability to bind to virtually all cell types and cause damage to several organs [67], lectins/agglutinins are sometimes categorized as food toxicants [68,69]. WGA IgG and IgA levels were significantly higher in patients with untreated Celiac disease compared to healthy controls [70].…”

Plant‐insect interactions: what can we learn from plant lectins?

“…Exogenously applied lectins disrupt the gut epithelium in vivo upon ingestion. Miyake et al (2007) attributed this to the lectin blocking normal membrane repair pathways. Although the literature on mammals is considerably ahead of our current knowledge of insect carbohydrate structures, work on insect glycans is rapidly growing.…”