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Lectins are proteins of non-immune origin that specifically interact with sugar molecules (carbohydrates) without modifying them. Lectins are found in a variety of species from plants to insects to man. They serve many different biological functions from the regulation of cell adhesion to glycoprotein synthesis and the control of protein levels in the blood. Lectins are also known to play important roles in the immune system by recognising carbohydrates that are found exclusively on pathogens, or that are inaccessible on host cells.

Lectins are often found in common foods, and many of them are blood type specific. Because cancer cells often manufacture copious amounts of antigens on their surface, many lectins will agglutinate them in preference to normal cells.

Specificity for human blood groups Blood typing; structural studies of blood group substances; identification of new blood types; diagnosis of secretors.
Toxicity in animals and humans Studies of nutritional value of foodstuffs
Induction of mitosis in lymphocytes Studies of chromosomal constitution of cells.
Agglutination of malignant cells Investigation of architecture of cell surfaces.
Precipitation of polysaccharides and glycoproteins Isolation, purification and structural studies of carbohydrate-containing polymers
Binding of sugars Studies of specific combining sites on proteins

Table 1. Properties and uses of lectins.


Carbohydrate Specificity

While it is relatively easy to describe what a lectin does, they represent such a large and diverse class of naturally occurring molecules that it would be impossible to come up with a description of any one lectin that would fit all others. In a simple sense, a lectin is a protein-based molecule with a ‘sweet tooth.’ By this we mean that most lectins are comprised at least in part by proteins synthesized by the living organism than made it. Lectins like to attach to carbohydrates, mainly sugars or glycoproteins. Many of these carbohydrates are found on the exterior walls or membranes of simple cells, where they constitute the outer markers, or antigens, of that living creature. The great majority of the plant lectins are present in seed cotyledons where they are found in the cytoplasm or in the protein bodies, although they have also been found in roots, stems and leaves. Not surprising, many of these seeds, stems and leaves are components of many common foodstuffs. Thus lectin ingestion as part of any normally balanced diet is virtually unavoidable.

Until recently, it was not recognized that nature could employ sugars for the synthesis of highly specific compounds that can act as carriers of biologic information. Monosaccharides can servo as "letters" vocabulary of biologic specificity, where the words are formed by variations In the nature of the sugars present, the type of linkage, and the presence or absence of branch points. The first proof that sugars could serve as specificity determinants came from the discovery that influenza virus could agglutinate red cells only in the presence of certain membrane-bound carbohydrates. It these were removed, the virus no longer could bind to the cell. Sugars on cell surfaces also seem to determine the distribution of the circulating cells within the body.

Radioactively treated rat lymphocytes will migrate to the spleen when re-injected into the animal. However if the sugar fucose is removed from the surface of the cells before reintroduction, the cells migrated to the liver instead, as if the fucose served as a ZIP code - directing the calls where to go. It was not until 1953 that we discovered that the specificity of the ABO blood group-system was determined by similar sugars. For example, the difference between blood types A and B lies in a simple sugar unit that sticks out from the end of a carbohydrate chain of a glycoprotein or glycolipid. In blood type A the determinant is N-acetylgalactosamine, in type O it is fucose, and in group B it is galactose.


When a lectin contains multiple binding sites, they can interconnect large numbers of cells, causing them to clump together or agglutinate. Each molecule of a lectin has two or more regions, perhaps clefts or grooves, each of which fits a complementary molecule of a sugar or several sugars. It is by means of these combining sites that the lectin attaches itself to the sugars on cell surfaces. Bacteria typically attach to prospective host cell membranes via receptors with lectin-like sugar specificity. This is of great importance, as the adherence of bacteria to host tissue surfaces is the initial event in a bacterial infection. Salmonella and Escherichia coli both carry several surface lectins with pronounced immunosuppressive ability. Both adhere to epithelial cells by attaching to the sugar mannose on the victim cell’s surface.

The attachment of lectins can often be blocked by the use of sugars specific to the lectin as a sort of ‘sacrificial molecule.’ For example, colonization of the urinary tract with E. Coli can markedly be reduced by the administration of mannose sugars, which is probably why cranberry juice works in preventing bladder infections, since it is an excellent source of mannose.

The binding of lectins to sugar is quite weak. It does not form a covalent bond, but is reversible, like enzyme-substrate or antigen-antibody reactions. Lectin-sugar reactions actually share many factors in common with antigen-antibody reactions, especially precipitation, which has prompted several investigators to suggest that lectins are plant antibodies. However this has been tempered by several major differences between the two. Antibodies are made by higher organisms which have specific immunologic organs. Lectins are present as constituent proteins. Second, antibodies are all structurally similar to one another, whereas lectins are structurally diverse; examination of the amino acid sequence, molecular size and other molecular properties show that lectins have little in common other than they are all proteins.

For example soybean agglutinin is a glycoprotein with no di-sulphide bond; its molecular weight is 120,000, It consists of four subunits and has two binding sites. Wheat germ agglutinin is not a glycoprotein and is rich in di-sulphide bonds with a molecular weight of 36,000, It has two identical subunits and four binding sites for sugars.


Naturally occurring agglutinins were first identified in 1888 by Herrmann Stillmark at the University of Dorpat in Estonia. While investigating the toxic effects on blood of castor bean extract (Ricinus communis) it was noticed that the red cells were being agglutinated. The material responsible for the agglutination was isolated and called ricin. Shortly afterward at the same university it was discovered that the toxic extract of the seed Abrus precatoris also caused cells to clump together. This new agglutinin was called abrin.

This immediately caught the attention of the German bacteriologist Paul Ehrlich who recognized that he could investigate certain immunologic problems with them rather than the then-popular bacterial toxins. With these two agglutinins some of the most basic principles of immunology were discovered. In 1908 Karl Landsteiner, who also discovered the basic ABO blood types, reported that small amounts of lentil lectin would agglutinate rabbit erythrocytes, even high concentrations of the lectin had no effect on pigeon red cells. Due to their peculiar properties, the lectins are used as a tool both for analytical and preparative purposes in biochemistry, cellular biology, immunology and related areas. In agriculture and medicine the use of lectins greatly improved in the last few years.

Blood Type Specificity

In 1945 William Boyd of the Boston University School of Medicine discovered that lectins can be blood group specific; some lectins being able to agglutinate the red cells of one type but not those of another. He discovered that lima bean lectin would agglutinate red cells of human blood type A but not those of O or B. It was Boyd who also was the first to coin the term ‘lectin’ which is Latin for legere, or ‘to choose.’ The seeds of Lotus Tetragonobolus can agglutinate group O specifically, and Bandairaea simplicofolia is specific to group B. The specificity of lectins is so sharply defined that they can differentiate among blood subgroups. Dolichos biflorens lectin reacts more vigorously with blood group Al than A2. Other blood groups can be distinguished by lectins, such as M and N blood types. Source

Endogenous Lectins

There is evidence that lectins may be involved in the recognition between cells or cells and various carbohydrate- containing molecules. This suggests that they may be involved in the regulating physiological functions. They seem to play an important role in the defense mechanisms of plants against the attack of microorganisms, pests, and insects. Fungal infection or wounding of the plant seems to increase lectins. Lectins are believed to be nature's own insecticides and because of this, they have attracted the attention of scientists who are genetically engineering them to produce food plants, containing specific lectins, which will not only have an insecticide effect, but on ingestion will also be 'hostile' to harmful bacteria in the human and animal gut. But that is another story.

It has increasingly been shown that the body uses lectins (or lectin-like molecules) to accomplish many of its most basic functions, including cell-to-cell adherence, the control of inflammation and the spread of cancer cells and even the programmed death of certain specific cells of the immune system.


Lectins in the Diet

Lectins are apparently most widely distributed in plants, where they were found in almost 1000 plants of some 3000 examined in recent years. They are particularly abundant in legumes and they account for between 1.5 and 3 percent of the total protein content of soy and jack beans. The second most common source of lectins are seafood.

Nachbar and Oppenheim also noted high levels of lectin activity in dry roasted peanuts, Corn Flakes, Rice Krispies, and Kellogg's Special K. The banana agglutinin was actually enhanced by heating, and was inhibitable by n-acetyl glucosamine (NAG) and N-acetylgalactosamine (blood group A antigen) glycoproteins.

Phytohemagglutinins from kidney beans can resist mild cooking and retain lectin activity even at 90 degrees C for 3 hours. Pre-soaking the beans however resulted in complete loss of lectin activity. Several investigators noted year-to-year and batch-to-batch variations in the lectin content of foods, so the occasional lectin is likely to occur even with foods normally considered safe.

Nachbar tested 88 common food items and reported erythrocyte agglutination activity in 38. Many foods showed agglutinating activity so substantial that the extracts could be diluted several fold. Crude extracts of various foods tomato, lettuce, cucumber, wheat bran and whole wheat, sesame and sunflower seeds, vanilla yogurt, coconut, banana and baby food banana, carrot, onion, apple, alfalfa and soya protein have also been found to bind, and in some instances precipitate the components of human saliva, including cellular debris and bacteria.

This may have some significance in the development of caries. Interestingly, avocado lectin inhibited the sucrose dependent adherence of S. mutans to plaque pellicle. Approximately 1 to 5% of the ingested dietary lectins are absorbed into the blood stream. Here they can clump and bind to red and black blood cells, destroying them. It has been proposed that much of the low grade anemias seen In the third world may be resulting from destruction of red blood cells by lectin rich grain and bean diets.

Resistance to Digestion

Although many lectins are destroyed by normal cooking (which is why grains and beans are edible), many are not. Relative resistance to lectins was part of the classic description of wheat germ agglutinin (WGA) made by Joseph Charles Aub in 1963. WGA as Freed points out is in fact one of the more heat sensitive lectins, being destroyed after 15 minutes at 75 degrees C, whereas other wheat lectins in gluten and gliandin resist autoclaving at 110 degrees C for 30 minutes. Gibbons and Dankers noted that in over 100 food plants found to contain active lectins, seven were autoclave resistant (apple, carrot, wheat bran, canned corn, pumpkin seeds, banana and wheat flour).

Lectins which are especially rich in di-sulphide bonds such as WGA are very resistant to proteolytic enzymes, detergents, urea, alkalis and acids. Foodstuffs are naturally rich in fiber and are an important cause of allergies. Dietary lectins also stimulate mast cells which can degranulate and release stored histamine, leading several researchers to ascribe a role for dietary lectins in the genesis of food allergy.


Lectins As Bioweapons


Georgi Markov

Gut Sensitization

However it is not generally known why some individuals become sensitized to food in their diets. In an attempt to clarify this, celiac disease has been extensively studied, since patients with this disease usually normalize when placed on a gluten free diet. Researchers reported that the mucous membranes of celiac patients showed sugar residues which were capable of binding to the lectins in wheat germ, which resulted In a cytotoxic reaction. Rats treated with Concavallin-A or wheat germ lectin developed a gut membrane that was paradoxically impermeable to small molecules, but very permeable to large, highly allergenic molecules, a situation which is mimicked in food allergies and celiac disease.

Lectins and Microbe Infection

The Thomsen-Friedenreich (T-Tn) antigen is generally not found on human cells, but can be exposed after the sialic acid molecule have been removed by the action of neuramidlase. This can commonly occur since all Pneumococci, most strains of influenza, Vibrio cholerae and Clostridium all contain active neuramidase. Antibodies against T antigen are found in humans after the first few months of life. Peanut agglutinin is specific for it. After neuramidase exposure, PNA binding sites for T-antigen can be found on lymphocytes, erythrocytes, breast epithelial cells, glomeruli, milk-fat globule membranes and thrombocytes, serum glycoproteins. Hemolytic-uremic syndromes following pneumoccocal infection, presumably an attack by anti-T antibodies, could possibly result from T-specific lectins. It also interesting to ponder the observation of several investigators who have noticed that many cases of food intolerance develop after influenza.

Bacteria typically attach to prospective host cell membranes via receptors with lectin- like sugar specificity. This is of great importance, as the adherence of bacteria to host tissue surfaces is the initial event in a bacterial infection. Salmonella and Escherichia coli both carry several surface lectins with pronounced immunosuppressive ability. Both adhere to epithelial cells through units of mannose on the cell surface. Colonization of the urinary tract with E. Coli can markedly be reduced by the administration of mannose sugars. Inhibition of bacterial adherence to bladder cells has been thought to account for the beneficial effects of cranberry juice. Cranberry juice cocktail inhibited the adherence of urinary isolates of E. Coli expressing type 1 fimbriae (mannose specific) and P fimbrae (specific for apha-d-gal-[1-4] beta-d-gal). Pineapple juice inhibited type 1 but not P type fimbrae. Lectins on type 2 fimbriae, which recognized galactose receptors on lymphocytes, play a crucial role in the phagocytosis of several Actinomyces spp.

Irritation of the gut mucosal tract by Salmonella lectin may be as important in the production of the symptoms of food poisoning as the salmonella food toxin itself. In sensitive individuals, lectins in the diet can bind to the intestinal walls, causing severe lesions, inflammation and swelling.

gonorrhea, the bacteria which causes the venereal disease gonorrhea, Is unique in that it is the only member of its family that is pathologic and the only member that is agglutinated by wheat germ agglutinin.

Several lectins have been shown to possess agglutination properties against bacterial strains. Staphylococcus aureus and mutans has been extensively studied, These have been shown to be agglutinated by several commonly available lectins- including tomato, cantaloupe and wheat. The author has employed tomato lectin in clinical practice by way of topical applications of raw tomatoes to the eyes in staphylococcal conjunctivitis with very satisfactory results.

Lectins have been shown to inhibit the release of Myxovirus and Newcastle Disease virus from infected cells.

Lectins and Malignancy

No other property of lectins has attracted as much attention as their ability to agglutinate malignant cells. This was discovered by chance at Massachusetts General Hospital by Joseph Charles Aub in 1963. Aub believed that the difference between cancer cells and normal cells lay on their surfaces; and that alterations in the properties of the cell surface enabled cancer cells to multiply when normal cells would not, detach from their primary site and spread throughout the body. At the time the idea seemed quite strange, and as Nathan Sharon, in his review article on lectins In Scientific American, put it: "bordered on lunacy".

Aub worked with several enzymes, trying to determine whether the surface of a malignant cell was different from that of a normal cell. Only in the case of one enzyme, a lipase from wheat germ, did he observe a difference. Normal cells did not seem to be affected, but malignant cells were agglutinated. When he replace the wheat germ lipase with a pancreatic lipase, however no agglutination took place. Aub also found that the enzyme activity of the wheat germ could be destroyed by heating, but the agglutination took place all the same. Aub and his colleagues then discovered that the wheat germ lipase contained as a contaminant a small protein that was responsible from the agglutinating activity.

Burger and Goldmanberg suggested that the surface of malignantly transformed cells contained a component which was not found on the surface of normal cells. It was proposed that this component is N-acetylglucosamine (NAG) or a closely related derivative since ovomucoid, a glycoprotein rich in NAGs inhibited the agglutination at very low concentrations. A higher local density of lectin binding sites have been observed in addition to an interesting phenomenon called "capping?" where lectins begin to cross link more and more surface receptors which result in more and more binding sites becoming available for cross linking. This eventual tends to cluster the binding sites to one side of the cell, producing a "cap" which can be observed by radio identification. This apparently results from a transmembrane effect involving a glycoprotein, spectrin, which aggregates upon contact with a lectin.

This discovery began a now era in lectin research. Soon it was found that Concanavallin-A also agglutinated malignant cells. Recently the Weizmann Institute of Science in Israel found that soybean agglutinin also possesses the same property. As a rule malignant cells are agglutinated by very low concentrations of a particular lectin and normal cells are not agglutinated unless the concentration is many times higher. The higher proportion of malignant cells agglutinated probably results from the sizeable increase in surface receptors on the malignant cells, which probably results from their incredibly high reproduction rate.

Peanut Agglutinin has been shown to inhibit the growth of several breast cancer cell lines, In addition to allowing for the destruction of breast cancer cell In harvested bone marrow with a highly effective and selective (3 or 4 log depending on the cell type) action.

Tags: [[tag:ABO Blood Group]] [[tag:Polymorphism]] [[tag:Antigens]] [[tag:Antibody]] [[tag:Lectins]] [[tag:Glycoproteins]]