Mannose/fucos receptor

Mannose/fucose receptor (a lectin)

Parasites bring bound biofilm (yours and theirs) with them as they secretly settle or sneakily travel and settle to farm us and our biofilm so they can lay eggs. 

Cells have proteins called receptors that bind to signaling molecules and initiate a response. Different receptors are specific for different molecules. Dopamine receptors bind dopamine, insulin receptors bind insulin, nerve growth factor receptors bind nerve growth factor, and so on. 

Hundreds of receptor types are found in cells, and varying cell types have different populations of receptors.  Receptors can also respond directly to light or pressure, which makes cells sensitive to physical events. 

There are various kinds, like glycoprotein and lipoprotein.  Hundreds of different receptors are known and many more remain undiscovered.  Almost all known membrane receptors are proteins that cross the membrane (1-7 times). 

A certain cell can have several membrane receptors while displaying various amounts.  A receptor may also exist at varying concentrations on different membrane surfaces, depending on function. Since receptors usually form “clusters” on the membrane surface, distribution is mostly heterogeneous. 

The macrophage expresses cell surface lectins with activities that support specific functional roles and corresponds to differentiation.   Besides about a half million marking glycoproteins and many MR, receptors exist for HSPs or AGEs, mannose-6-phosphate, β-glucan, sialoadhesin and several others that bind to galactose. 

Human peripheral blood low density mononuclear cells cultured in granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 develop into dendritic cells (DCs) that are extremely efficient in presenting soluble antigens to T ceils. 

DCs respond to TNF or, CD40 ligand, IL-1, and LPS with changes that include down-regulation of macropinocytosis and Fc receptors, disappearance of class II compartment, and up-regulation of adhesion and co-stimulation. 

These changes occur within 1-2 days and are irreversible, since neither pinocytosis nor the class II compartment are recovered when the maturation-inducing stimulus is removed. The specificity of the MR and the capacity to respond to inflammatory stimuli maximize the capacity of DCs to present infectious non-self antigens to T cells.

Receptors are generally transmembrane proteins, which bind to extracellular signaling molecules and then transmit the message through a sequence of molecular switches to internal signaling pathways. 

Membrane receptors fall into three major classes: G-protein-coupled, ion channel and enzyme-linked.  Since membrane receptors interact with both extracellular signals and molecules within the cell, they permit signals to affect cell function without actually entering.  Most signaling molecules are too big or too charged to cross a membrane.

Not all receptors exist on the exterior of the cell.  Some receptors are deep inside, even in the nucleus. These receptors typically bind to molecules that can pass through the plasma membrane, gases like nitrous oxide as well as fats and steroids.

Agglutination (binding) of different sugars on the about a half million glycoprotein lectins that mark individual cells by crossing cell membranes determines human blood type.  Although a few lectins are hormetic, identifying excess irritating lectins can help define a lower stress diet.

The mannose receptor (MR) can cause internalization of compounds that are recognized by three cysteine-dependent binding sites. The MR is subject to proteolytic processing and glycosylation, has a complex expression pattern and has tissue-dependent binding properties.  The MR is important in homeostasis, like clearance of endogenous products (hormones) and cell adhesion, as well as pathogen recognition and antigen presentation. 

The innate immune system is the first line of defense against invading pathogens. Innate cells recognize microbes via pattern recognition receptors (PRRs) initiate innate immune responses; and eventually trigger adaptive immunity. Association of heterologous PRRs synergistically enhances their signal intensity. Such PRR cluster formation is essential for generating anti-fungal immunity.

Relative to viruses and bacteria, sizes of fungi are, in general, significantly larger. It is therefore logical for host cells to form PRR clusters in an effort to maximize the interaction between PRRs and the fungal surface. 

CD206 is widely known as the MR, or more precisely as the mannose receptor C type 1 (MRC1).  The MR is a 162-175 kDa type -1 transmembrane protein and a member of the Group VI C-type lectins along with CD280 (ENDO180), CD205 (DEC205, and the phospholipase A2 receptor. Cells can increase or decrease the number of receptors to alter sensitivity, as a locally acting feedback mechanism. 

The MR is a heavily glycosylated endocytic receptor that recognizes both mannosylated and sulfated ligands.  MR function is altered through proteolytic cleavage and changes in glycosylation and conformation. 

G protein-coupled receptors are a large protein family of transmembrane receptors, and are characteristic of eukaryotic membranes.  The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, sugars, and neurotransmitters, and vary in size from small molecules to large proteins. The effect created is usually bewilderingly biphasic.

Heat shock proteins (HSPs) are mimicked by dietary or smoked advanced glycosylation end-products (AGEs).  HSPs or AGEs bind to antigen presenting cells and are internalized spontaneously by receptor-mediated endocytosis.  There is also co-localization of internalized HSPs and surface MHC class I molecules in early and late endosomes.

In healthy brain, MRs cannot be detected in oligodendrocytes, ependymal cells, endothelial cells or parenchymal microglia. The MR is expressed by perivascular macrophages/microglia and meningeal macrophages, where it seems important for  immune defense, and by two populations of brain cells, astrocytes and neurons.

The developmentally dependent, regionally regulated expression of MR in glial and neuronal cells suggests that the MR plays an important role in homeostasis during brain development and/or neuronal function.

Bacteria (and our cells) use sugars to communicate.  Sugars trigger changes in bacteria.  Sugar use in living communication systems is called glycobiology.  Mannose, galactose, fucose, xylose, N-acetylglucosamine, N-acetylneuraminic acid, N-acetylgalactosamine and other sugars are used to make structure, regulate as well as signal. 

The specific binding of N-acetylneuraminic acid to wheat-germ agglutinin (WGA) is based on configuration similarities between N-acetylneuraminic acid and N-acetylglucosamine.

Lectins are widespread in the plant kingdom, and are anti-nutrients in food. Cereal grain lectins are called WGA.  WGA can interfere with digestive/absorptive activities and can shift the balance in bacterial flora. 

WGA stimulates pro-inflammatory messengers, even at very low concentrations.  WGA  binds to and activates white blood cells.  WGA crosses the blood-brain barrier and attaches to myelin. It can inhibit nerve growth factor, important for growth, maintenance and survival of neurons.  WGA may induce apoptosis.  

WGA binds to, interacts and disrupts a basic component found within all neural, connective and epithelial tissue (n-acetyl-glucosamine).  Once WGA makes it through the mucosa and/or digestive lining, it can exert systemic effects which are easily overlooked.

One way to gauge the pervasive adverse effects of WGA is the popularity of glucosamine. Its main source is from acetyl-glucosamine-rich chitin of crustaceans, like shrimp and crab.  Glucosamine effectively reduces pain and inflammation by binding with WGA.

Chitins are long polymers of n-acetyl-glucosamine, the primary binding target of WGA.  WGA and "chitin-binding lectin" share functional similarities.  Besides WGA-rich wheat, these chitin-binding lectin containing foods are: potato, tomato, barley, rye and rice. 

WGA sits on the leptin receptor for a really long time, though it doesn’t elicit the same downstream signaling effects.  WGA is one of the most widely used lectins in cell biology. WGA contributes to leptin resistance and other metabolic issues (like insulin resistance).  WGA crosses the blood brain barrier.

Sugars are the "letters of the cellular alphabet." These markers exist on cell surfaces and help communicate.  These sugars are used by pathogens to enhance virulence in many subversive ways.  Instead, intelligent use of 6-carbon mannitol, or 5-carbon xylitol reduces both biofilm virulence and modulates host inflammatory response.  

After eating fructose, a functional ketone, metabolic burden falls on the liver.  Glucose (dextrose), which acts as an aldehyde, is used by every cell as "blood sugar."  Much glucose is "burned up" immediately (the liver processes about 20%).  

Instead, fructose is turned into free fatty acids (FFAs), VLDL (the damaging form of cholesterol) and triglycerides, which get stored as fat.  The fatty acids created during fructose metabolism accumulate as fat droplets, causing insulin resistance and liver inflammation. Insulin resistance progresses to metabolic syndrome and type II diabetes.  

Fructose is the most lipophilic carbohydrate and converts to activated glycerol (g-3-p), which turns FFAs into triglycerides. The more g-3-p, more fat stored.  When glucose is eaten, less than 1% is stored as fat, however 1/3 of fructose becomes fat.  

The metabolism of fructose is like ethanol and creates many waste products and toxins (ROS), which have a biphasic effect, inducing beneficial hormesis with perceived mild, intermittent stress or similar excessive chronic stress (over an individual threshold).  

Glucose suppresses ghrelin (hunger hormone) and stimulates appetite-lowering leptin.  Fructose has little effect on ghrelin and interferes with leptin, resulting in overeating.  Sucrose is a disaccharide composed of glucose and fructose.  We use glucose as our primary energy source and the excess energy from fructose is used in fat synthesis, which is stimulated by the insulin released in response to glucose.

Mannose and glucose are different variants of sugars.  Both are monosaccharides, but but they differ in chemical structure and look.  The hydroxyls on carbon 2 in glucose are headed in the same direction as hydroxyls on carbon 4 and 5, while in mannose, the hydroxyls on carbon 2 point in the same direction as the hydroxyl on carbon-3.

Mannose is different from other 6-carbon rings of sugar like fructose, lactose and table sugar (sucrose).  Glucose is stored for carrying out various energy-dependent processes, while its stereoisomer mannose  increments immune response.  Mannose is involved in many metabolic transformations being added to glycoproteins and glycolipids or formed into fucose incorporated into glycoproteins.

The primary source of mannose is glucose.  Mannose is absorbed from the GI tract of rats at only about 12% the rate of glucose.  Three naturally occurring aldohexoses are glucose, mannose and galactose.

Molecules of bacteria, viruses, and toxins have receptor sites that are drawn to sugars on particular cells and can hang onto them.  This allows bacteria to stick to the surface of cells.  If bacteria (and viruses) cannot stick, normal cleansing washes them out. 

The MR is a carbohydrate-binding receptor expressed by selected populations of macrophages and dendritic cells (DCs) and nonvascular endothelium (like the bladder, mouth or sinuses).

Carbohydrate recognition by MR facilitates macrophage uptake of bacteria, yeast and parasites, part of innate immunity. MR is also important in adaptive immunity, partly by bringing antigens to MHC class II–containing compartments in immature dendritic cells for processing, and by delivering the attacker's glycolipids to endosomes in T cells.  

Organelles in the endocytic pathway are composed of a mosaic of structural and functional regions. These regions consist, at least in part, of specialized protein–lipid domains within the plane of the membrane, or of protein complexes associated with specific membrane lipids. 

The capability to take up mannosylated protein antigens is important for the biologic function of epidermal dendritic cells, as many glycoproteins derived from bacteria and fungi are mannosylated.

The MR is an integral membrane protein expressed on the surface of tissue macrophages, skin cells and endothelial cells.  MRs are also on fibroblasts and keratinocytes.  The MR is part of a family of endocytic receptors.  After binding to mannose-rich conjugates or pathogens, the MR mediates endocytosis.

Many pathogens use binding at the MR to enhance virulence.  Without this settling, pathogens, viruses to parasites, can't enter the cell and/or won't create an inflammation-inducing biofilm.  Leishmania donovani uses a MR on macrophages to establish intracellular parasitism.

The cell walls of each E. coli are covered with tiny fingers called fimbria, which allows them to "stick" to the bladder walls and even work their way up to ureter and kidneys.  Because they cling, they can't simply be washed out with urine.  Fimbria are made of an amino acid-sugar complex, a glycoprotein called lectin, which makes them sticky.

Lectin on the bacteria's fimbria binds to mannose, which is made by your cells and covers  internal linings (like throat, sinuses and urinary organs).  Mannose allows pathogens to adhere (like Velcro).  

Increased binding to epithelial cells from non-secretors occurs regardless of blood group.   Being able to secrete more immunoglobulins or blood type into saliva, mucus or other fluids, gives more  protection, especially from microorganisms and lectins.  Secretor status determines IgA concentrations and is significant in streptococcal throat infections. Non-secretors have more risk to rheumatic fever and rheumatic heart disease.

Another advantage of being a secretor is promotion of a stabilized, blood-type friendly biofilm.  Many friendly bacteria actually use blood type as one of their preferred foods.  Secretors have a steady supply of blood type in mucus; their beneficial bacteria have a much more constant food supply.

D-mannose 'sticks' to E. coli lectins even better than E. coli lectins adhere to human cells. When one takes a large quantity of D-mannose, almost all spills into the urine, 'coating' E.coli so they can no longer adhere.  The E. coli are literally rinsed away. 

The MR is used by a coronavirus during URT infections.  MR is a binding receptor, which requires a partner (to trigger phagocytosis or other function).

The MR or mannose-binding lectin (MBL) or mannan-binding protein attaches to sugars.  Lectins activate complement (an immediate defense against infection, which is pro-inflammatory); it is part of innate and adaptive immunity.  MBL is versatile, it functions like IgM, IgG and C1q.  MBL is important in early infection and primary in innate immunity.  

Rheumatoid arthritis is described as a systemic inflammatory auto-immune disease that is partly genetic. The innate immune complement protein mannose binding lectin (MBL) and their MBL2 genetic variants are linked with different infectious and autoimmune diseases.

Parts of the alternative and classical complement pathways contribute to brain injury after ischemia and reperfusion.  Inhibition of these pathways is protective.  Inhibition of the MR decreases infarction size after ischemic stroke and reperfusion.

Without this binding, mobile white blood cells won't settle and become inflammatory cytokine-spewing mast cells.  The MR fuels immune response, like allergies. 

Protein O-mannosylation is common, but few such glycoproteins have been described.  The important cadherin and plexin families of cell membrane receptors are O-mannosylated. The mannose-binding lectin 2 gene is polymorphic and codes for a protein important in innate immunity.  Gene variants are linked with many diseases.

The MR is non-specific and toll-like.  This receptor is one of many of Nature's strategies present in garlic, carrots and berries.  It is a C-type lectin carbohydrate binding protein primarily present on the surface of our macrophages and dendritic cells.  

The MR can be detected in the circulation, including sulfated glyccoprotein hormones and glycoproteins released in response to pathologies.  The MR recycles continuously between the plasma membrane and endosomal compartments.

Bacteria causing infections like to bind to d-mannose on the cell membranes of tissue.  D-mannose is a monosaccharide sugar in fruits and is similar to glucose except in its three-dimensional form (stereochemistry).  Our body can convert glucose to mannose.

Glucose and sucrose are agonist and mannose is antagonist to the G protein-coupled MR in yeast.  

Expression of macrophage MR is inhibited by interferon y (a T helper type 1 lymphokine). 

Interleukin 4, made by Th-2 lymphocytes, up regulates major histocompatibility class II antigen but inhibits inflammatory cytokines made by macrophages.  Murine interleukin 4 enhances macrophage MR expression (10X) and activity (15X).

Mannose in the intestine is involved in immunological reactions.  In intestinal infections, dietary d-mannose competes with the d-mannose on the GI cells and allows bacteria to leave their binding sites and attach to the d-mannose in fruit and lessen the infection.

Xylitol is used in many ways and as a sweetener; (2-14 teaspoons/day) reduces tooth decay, sinus and upper respiratory tract infections (URTs) and urinary tract infections (UTIs) as well as diarrhea.  The right amount cures constipation; too much leads to flatulence and loose bowels.

Bacteria and viruses involved with gut pathology provoke an immune response (inflammatory products are pathogenic biofilm's favorite food).  Bacterial cell walls bind to mucosal cells (of the urinary and respiratory tracts and of the gut) via MRs.  Lectins bind to d-mannose. 

D-mannose is present in fruit and is there in lesser amounts than the monosaccharides, glucose and fructose.  Besides the mannose made in cells of the GI tract, It is also in fruit (peaches, pineapple, apples, oranges and berries (cranberries and blueberries).

Filling the MR is one strategy in ingesting sugar alcohols like xylitol.  Sugars made of rings of five carbons also make structurally weaker biofilms and aren't metabolized by most pathogens.

Unsweetened cranberry (or tart cherry) juice can be diluted in water.  Pomegranates taste sweet and sour.  Pomegranates destroy worms in the intestinal tract.  Eat them raw, away from regular meals.  Leishmania donovani uses a MR on our phagocytes to establish intracellular parasitism. 

The most active ingredient in cranberry juice is D-mannose.  D-mannose can actually be derived from berries, peaches, apples and other plants. So why not drink cranberry juice instead of taking sugary D-mannose?

The amount of D-mannose in cranberry juice is much less. Plus, cranberry juice is high in other sugars, which adds stress to the immune system and fuels pathogens.  D-mannose is 10-50 times stronger, non-toxic and has no adverse effects.

Unlike large amounts of fructose one gets with cranberry juice, D-mannose does not convert to glycogen or get stored in the liver.  Only very small amounts of D-mannose are metabolized, so it doesn't interfere with blood sugar or produce metabolic stress. 

D-mannose is more like glucose, which every cell uses (but D-mannose is absorbed much more slowly).  Most of the D-mannose is filtered through the kidneys and routed to the bladder, then quickly excreted in urine, making it ideal for those with diabetes or anyone who is not interested in drinking sugary fruit juice.

Carrot juice or the veggie eaten plain also kills parasites.  Carrots contain an essential oil that destroys roundworms and pinworms.  Grated carrots work best on an empty stomach.