Lectin Research Abstracts

Dietary lectins are metabolic signals for the gut and modulate immune and hormone functions.

Eur J Clin Nutr 1993 Oct;47(10):691-699 
Pusztai A
Rowett Research Institute, Bucksburn, Aberdeen, UK. 

Although it is common knowledge that some dietary lectins can adversely affect the growth and health of young animals and that, therefore, lectins are implicated in nutritional disorders of the digestive system, it has not been rigorously established that findings with animals are also directly applicable to humans. However, because the glycosylation state of the human gut is basically similar to that of higher animals, it may be confidently predicted that the effects of dietary lectins will have similarities in both humans and animals. Most lectins in our diet are resistant to breakdown during gut passage and are bound and endocytosed by epithelial cells. These lectins are powerful exogenous growth factors for the small intestine, can induce dramatic shifts in its bacterial flora and interfere with its hormone secretion. In addition, lectins which are transported across the gut wall into the systemic circulation can modulate the body's hormone balance, metabolism and health. Although these physiological effects are mediated or reinforced by immune responses, they are primarily the result of the specific chemical reactivity of lectins with cell surface receptors of the gut.

Lectins in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature.


Nachbar MS, Oppenheim JD
Am J Clin Nutr 1980 Nov;33(11):2338-2345 

Plant lectins or phytohemagglutinins possess potent in vivo biological activities. Some, primarily of the family Leguminosae, have been shown to have deleterious nutritional effects. Little information exists, however, regarding the prevalence of lectins or the specific foods that contain lectins in the United States diet. In the present study the edible parts of 29 of 88 foods tested, including common salad ingredients, fresh fruits, roasted nuts, and processed cereals were found to possess significant lectin-like activity as assessed by hemagglutination and bacterial agglutination assays. Based on this survey and a review of the literature we conclude that dietary exposure to plant lectins is widespread. The spectrum of nutritional consequences of such exposure remains to be determined. 
 

Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils.


Eur J Immunol 1999 Mar;29(3):918-27
Haas H, Falcone FH, Schramm G, Haisch K, Gibbs BF, Klaucke J, Poppelmann M, Becker WM, Gabius HJ, Schlaak M.
Forschungszentrum Borstel, Germany. hhaas@fz-borstel.de

Dietary lectins, present in beans and other edible plant products, pose a potential threat to consumers due to their capacity to induce histamine release from basophils. In this study, we analyzed the capacity of 16 common, in particular dietary, lectins to induce human basophils to secrete IL-4 and IL-13, the key promoters of Th2 responses and IgE synthesis. Several of the lectins, especially concanavalin A, lentil lectin, phytohemagglutinin, Pisum sativum agglutinin and Sambucus nigra agglutinin, triggered basophils to release IL-4 at concentrations of up to 1 ng/10(6) basophils. Lectins with high IL-4-inducing capacity also stimulated the release of IL-13 and histamine. Lectin-induced IL-4 and IL-13 release reached a maximum after 4-6 h and more than 18 h, respectively. Affinoblotting revealed that lectins with the capacity to induce mediator release bind to IgE, suggesting IgE binding as initial step of signal generation. In conclusion, several dietary lectins can trigger human basophils to release IL-4 and IL-13. Since lectins can enter the circulation after oral uptake, they might play a role in inducing the so-called early IL-4 required to switch the immune response towards a Th2 response and type I allergy.

Modulation of immune function by dietary lectins in rheumatoid arthritis.

Br J Nutr 2000 Mar;83(3):207-17  
Cordain L, Toohey L, Smith MJ, Hickey MS.
Department of Health and Exercise Science, Colorado State University, Fort Collins 80523, USA. cordain@cahs.colostate.edu

Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.

Characteristics and consequences of interactions of lectins with the intestinal mucosa.

Pusztai A
Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK.
Arch Latinoam Nutr 1996 Dec;44(4 Suppl 1):10S-15S

Lectins are essential and omnipresent plant (glyco)protein constituents and are ingested daily in appreciable amounts by both humans and animals. As they are biologically highly active, their consumption may have serious consequences for metabolism and health. Lectins, by virtue of their stability and specific recognition and binding by gut brush border epithelial cells, are potent exogenous metabolic growth signals for the gut and the body. As a result of their binding to surface glycans they may affect the turnover and loss of epithelial cells, damage the luminal membranes of the epithelium, interfere with their digestive/absorptive activities, stimulate shifts in the bacterial flora and modulate the immune state of the digestive tract. When eaten in relatively large quantities, these lectins have appreciable antinutritive effects for the consumers. In contrast, lectins which are not bound by the mucosa usually induce little or no harmful effects. From recent studies it is now realized that in addition to the major and sometimes dramatic effects of lectins on the gut which are mediated through their binding to pre-existing membrane glycosyl groups, lectins as metabolic signals, can also radically alter the state of glycosylation of the gut epithelium and thus further amplify their potent physiological effects. Accordingly, with the judicious use of dietary lectins it is now possible "to engineer' the digestive tract for improved physiological performance and bacterial ecology.

Lectins and the intestine.

Torres-Pinedo R.
J Pediatr Gastroenterol Nutr 1983 Nov;2(4):588-94 

Lectins are being used increasingly for the study of carbohydrate structures in the small and large intestine. These substances are particularly useful for characterization of normal and abnormal intestinal mucus, but they are also important probes for investigation of epithelial surface changes associated with differentiation and maturation. Lectins are contained in significant amounts in a great variety of products ingested in the human diet. This, and the demonstration of their harmful effects on intestinal epithelium in rodents, indicate a need for investigation of potential adverse actions of lectins on human intestine.

Immunological aspects of the potential role of dietary carbohydrates and lectins in human health.

Eur J Nutr 1999 Jun;38(3):107-17  
Kilpatrick DC.
Department of Transfusion Medicine, South-East Scotland Blood Transfusion Centre, Edinburgh, Great Britain.

BACKGROUND: Little is known regarding the immunobiology of dietary carbohydrate intake and its relevance to human health, although foodstuffs contain many simple and complex carbohydrates. SYNOPSIS: Lectins, immunoglobulins, viruses, bacteria and host cells interact with each other forming a delicate equilibrium within the alimentary canal which may be perturbed by saccharide intake. The ways in which these components may interact at different sites within the alimentary canal are discussed, as are the possible influences on mucosal immunity and the induction of oral tolerance. The possible systemic influences of absorbed saccharides at loci remote from the gut are considered in terms of inhibition of dietary and endogenous lectins, inhibition of bacterial attachment, and alteration of leukocyte homing behaviour. Finally, possible means by which dietary carbohydrates might modify various specific diseases are considered. CONCLUSIONS: It is probable that dietary carbohydrates can alter the equilibria between lectins, secretory IgA and micro-organisms in the alimentary canal, and this consideration could be exploited to promote health. The possible effects of dietary saccharides on allergy/oral tolerance or on recognition events at gut-remote sites warrant further investigation.

Role of complement in the toxicity of dietary legumes.

Forsdyke DR.
Med Hypotheses 1978 Mar-Apr;4(2):97-100  

On the basis of in vivo data Jayne-Williams (1) has proposed that the toxicity of dietary legumes is due to their content of lectins which are immunosuppressive. On the basis of in vitro data with cultured lymphocytes (2), it is now proposed that ingested lectins bind to cell surfaces and cause autologous complement components to bind to and destroy immunologically competent cells. The hypothesis throws a possible light on the aetiology of favism and Whipple's disease.

Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins.

Br J Nutr 1993 Jul;70(1):313-321 
Pusztai A, Ewen SW, Grant G, Brown DS, Stewart JC, Peumans WJ, Van Damme EJ, Bardocz S
Rowett Research Institute, Bucksburn, Aberdeen. 

Incorporation of N-acetylglucosamine-specific agglutinins from wheat germ (Triticum aestivum; WGA), thorn apple (Datura stramonium) or nettle (Urtica dioica) rhizomes in the diet at the level of 7 g/kg reduced the apparent digestibility and utilization of dietary proteins and the growth of rats, with WGA being the most damaging. As a result of their binding and endocytosis by the epithelial cells of the small intestine, all three lectins were growth factors for the gut and interfered with its metabolism and function to varying degrees. WGA was particularly effective; it induced extensive polyamine-dependent hyperplastic and hypertrophic growth of the small bowel by increasing its content of proteins, RNA and DNA. Furthermore, an appreciable portion of the endocytosed WGA was transported across the gut wall into the systemic circulation, where it was deposited in the walls of the blood and lymphatic vessels. WGA also induced the hypertrophic growth of the pancreas and caused thymus atrophy. Although the transfer of the gene of WGA into crop plants has been advocated to increase their insect resistance, as the presence of this lectin in the diet may harm higher animals at the concentrations required to be effective against most pests, its use in plants as natural insecticide is not without health risks for man. 

Lectins and also bacteria modify the glycosylation of gut surface receptors in the rat.

Glycoconj J 1995 Feb;12(1):22-35 
Pusztai A, Ewen SW, Grant G, Peumans WJ, Van Damme EJ, Coates ME, Bardocz S
Rowett Research Institute, Bucksburn, Aberdeen, UK. 

Oral exposure to lectins or the presence or absence of bacteria in the small intestine were shown by histological methods using anti-lectin antibodies or digoxigenin-labelled lectins to have major effects on the state of glycosylation of lumenal membranes and cytoplasmic glycoconjugates of epithelial cells. Taken together with the dramatic effects of exposure to lectins on gut function, metabolism and bacterial ecology, this can be used as a basis for new perspectives of biomedical manipulations to improve health. 

Relationship between survival and binding of plant lectins during small intestinal passage and their effectiveness as growth factors.

Digestion 1990;46 Suppl 2:308-316 
Pusztai A, Ewen SW, Grant G, Peumans WJ, van Damme EJ, Rubio L, Bardocz S
Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK. 

The effects on the small intestine and the growth of rats of six pure plant lectins: PHA (Phaseolus vulgaris); SBL (Glycine maxima); SNA-I and SNA-II (Sambucus nigra); GNA (Galanthus nivalis) and VFL (Vicia faba), covering most sugar specificities found in nature, were studied in vivo. Variable amounts, 25% (VFL) to 100% (PHA, GNA) of the lectins administered intragastrically, remained in immunochemically intact form in the small intestine after 1 h. All lectins, except GNA, showed binding to the brush border on first exposure, although this was slight with VFL. Thus, binding to the gut wall was not obligatory for resistance to proteolysis. Exposure of rats to lectins, except VFL, for 10 days, retarded their growth but induced hyperplastic growth of their small intestine. The two activities were directly related. PHA and SNA-II, whose intestinal binding and endocytosis was appreciable after 10 days of feeding the rats with diets containing these lectins and similar to that found on acute (1 h) exposure, were powerful growth factors for the small intestine. 

The nutritional toxicity of Phaseolus vulgaris lectins.

Proc Nutr Soc 1979 May 1;38(1):115-120 
Pusztai A, Clarke EM, King TP

In rats fed on beans (Phaseolus vulgaris) the poorly digestible lectins were shown to react with intestinal cells in vivo and to cause a disruption of many of the brush borders of duodenal and jejunal enterocytes. Although depressed to a certain extent, absorption still occurred, probably through the non-disrupted cells of the small intestine. In addition, abnormal absorption of potentially harmful substances, lectin-related or of bacterial origin, could also occur, possibly as a direct effect of the disruption caused by the lectins on the enterocytes. It is suggested that toxicity was the result of ensuing systemic effects, such as for example the observed high N excretion possibly through increased tissue catabolism.




Toxicity of kidney bean (Phaseolus vulgaris) in rats: changes in intestinal permeability.


Digestion 1985;32(1):42-46 
Greer F, Pusztai A

Rats fed on diets containing kidney bean showed increased intestinal permeability to intravenously injected 125I-labelled rat serum proteins after an intragastric challenge with bean proteins. The enhanced accumulation of radioactive serum proteins in the lumen and walls of the small intestine indicated increased vascular permeability. It is suggested that dietary lectins may, at least in part, be responsible for this loss of serum proteins and thus contribute towards the overall toxicity of kidney bean proteins. 





Effect of dietary sub-lethal doses of lima bean lectin on relative organ weights, pancreatic and intestinal trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) in the rat.

Nahrung 1989;33(4):355-360
Aletor VA
Department of Animal Production and Health, Federal University of Technology, Akure, Nigeria. 

The dietary implications of feeding sub-lethal doses of extracted and purified lectin from lima bean were assessed in weanling rats using changes in relative organ weights, pancreatic and intestinal trypsin and chymotrypsin activities as the response indices. Liver weights decreased significantly (p less than 0.05) while the heart showed a slight but non-significant increase in response to dietary lectin levels. The kidneys, pancreas and spleen were not significantly affected by dietary lectin. Although the activities of the pancreatic enzymes tended, for the most part, to decrease with increasing dietary lectin, such decreases were not significant when compared with the control. 

Dietary antigens and primary immunoglobulin A nephropathy.

J Am Soc Nephrol 1992 Apr;2(10 Suppl):S173-S180 
Coppo R, Amore A, Roccatello D
Nephrology and Dialysis Department, Regina Margherita Children's Hospital, Turin, Italy. 

To investigate the role of dietary components in immunoglobulin A mesangial nephropathy (IgAGN), this study focused on gliadin, based on the reported association between coeliac disease and IgAGN as well as the pilot observation that a gluten-free diet was able to reduce the levels of circulating IgA immune complexes (IgAIC). Several gluten lectinic fractions modulate leukocyte oxidative metabolism, cytotoxicity, and chemotaxis. In IgAGN patients, serum IgA to dietary Ag were sporadically positive and IgAIC containing IgA to dietary components were significantly increased. The affinity of serum IgA to various lectins was increased in some patients. A gluten-free diet, given to IgAGN patients with high levels of circulating IgAIC and positive antigliadin IgA, was followed by a decrease in the mean levels of both IgAIC and IgA to various dietary Ag, parallel to a reduction in proteinuria. These data suggest that dietary components, such as Ag or lectins, may play a role in IgAGN by promoting IgAIC formation and perhaps favoring mesangial localization via lectinic interactions. 

Effect of kidney bean (Phaseolus vulgaris) toxin on tissue weight and composition and some metabolic functions of rats.

Br J Nutr 1985 Jul;54(1):95-103 
Greer F, Brewer AC, Pusztai A

Inclusion of kidney bean (Phaseolus vulgaris) proteins in the diet for rats was shown to affect the weight of some internal organs. Of these, in addition to the well-known hypertrophy of the pancreas attributable to dietary trypsin inhibitors, the observed atrophy of the thymus and the doubling in weight of the small intestine are related to the protein or lectin content of the bean diet, or both. Changes in tissue composition of the small intestine were also recorded. Its protein content increased by about 40-50% and carbohydrate content doubled suggesting the occurrence of increased mucinous glycoprotein secretion. Increased DNA content (by about 30-40%) however also indicated mucosal hyperplasia. The results gave further support to previous suggestions that the oral toxicity of kidney-bean lectins involves local reactions in the small intestine in combination with their effects on the systemic immune system and general metabolism. 

Natural human antibodies to dietary lectins.


FEBS Lett 1996 Nov 18;397(2-3):139-142 
Tchernychev B, Wilchek M
Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel. 

Natural antibodies to self and non-self proteins, including dietary proteins, are a significant part of the immune repertoire of humans. Antibodies to three structurally related legume lectins (Erythrina corallodendron lectin (ECorL), peanut agglutinin (PNA), and soybean agglutinin (SBA)) and to one cereal lectin (wheat germ agglutinin (WGA)) were purified by affinity chromatography from human sera and their binding specificity examined. The anti-SBA, anti-ECorL and anti-WGA antibodies exhibited high specificity, whereas the anti-PNA antibodies were polyreactive. Although the anti-WGA antibodies were highly specific for WGA, they also crossreacted with some other proteins. Although the anti-SBA and anti-ECorL antibodies both exhibited specificity when interacting with native lectins, they bound to a wider range of denatured lectins, indicating a common or universal epitope which is recognized by many natural antibodies. Interestingly, the natural antibodies did not interfere with the agglutination properties of the lectins. These findings may provide a basis for studying the in vivo biological effects of anti-dietary protein antibodies, including those against carbohydrate-binding proteins. 

Effect of phytohaemagglutinin on intestinal cell proliferation. Role of polyamines.

Arch Latinoam Nutr 1996 Dec;44(4 Suppl 1):16S-20S
Bardocz S, Rowett Research Institute, Aberdeen, Scotland, UK. 

The polyamines, putrescine, spermidine and spermine, mediate the effects of hormones and growth factors as second messengers. They are necessary for every step of protein, RNA and DNA synthesis and are therefore essential for cell growth and proliferation. As with hormones and peptide growth factors, plant lectins which bind to cell surface receptors of the brush border membrane are powerful extraneous growth factors for the gut and as a result, by interacting with brush border epithelial receptors, induce extensive proliferation and changes in the metabolism of epithelial cells via activation of second messenger pathways.These metabolic changes require vast amounts of polyamines, mostly spermidine. Thus, one of the first effects of the PHA signal is to stimulate the basolateral polyamine uptake system for the sequestration of polyamines from blood circulation in sufficient amounts to sustain the growth of the tissue.