Mast Cells (Part 1): Stabilize Mast Cells and Remove Brain Fog

It could be an allergy or there may be an invisible orchestra.

In allergic reactions, mast cells remain inactive until an allergen binds to IgE already coated upon the cell. R

Allergens are proteins or polysaccharides. Allergens bind to antigen-binding sites, which are situated on regions of the IgE molecules on a mast cell' surface. Binding of two or more IgE molecules, or cross-linking, is required to activate the mast cell. R

The clustering of the intracellular domains of the cell-bound Fc receptors, which are associated with the cross-linked IgE molecules, causes a complex sequence of reactions inside the mast cell that lead to its activation. This may have evolved as a defense system against parasites and bacteria. R

Granules and Mediators

Mast cell mediators are released through degranulation following the activation of the mast cells surface receptors. This list are examples of mediators that are released during mast cell degranulation include: R R R

• preformed mediators (from the granules):

  • serine proteases, such as tryptase and chymase

  • histamine

  • serotonin

  • proteoglycans, mainly heparin (active as anticoagulant) and some chondroitin sulfate proteoglycans

  • adenosine triphosphate (ATP)

• lysosomal enzymes

  • β-hexosaminidase

  • β-glucuronidase

  • arylsulfatases

• newly formed lipid mediators (eicosanoids):

  • thromboxane

  • prostaglandin D2

  • leukotriene C4

  • platelet-activating factor

• cytokines

  • TNF-α

  • basic fibroblast growth factor

  • interleukin-4

  • stem cell factor

  • chemokines, such as eosinophil chemotactic factor

• reactive oxygen species

Enzymes

• Lyn tyrosine kinase - Phosphorylates the ITAMs in the FcεR1 β and γ chain in the cytoplasm. It causes Syk tyrosine kinase to get recruited to the ITAMS located on the γ chains. This causes activation of the Syk tyrosine kinase, causing it to phosphorylate

• Syk tyrosine kinase - Targets multiple proteins and causes their activation

• Phospholipase C - Catalyzes Phosphatidylinositol 4,5-bisphosphate

• Inositol trisphosphate - Elevates calcium levels

• Diacylglycerol - Activates protein kinase C

• FYN - Phosphorylates Grb-2-associated-binder-like-protein

• Grb-2-associated-binder-like-protein - Binds to phosphoinositide 3-kinase

• Phosphoinositide 3-kinase - Activates protein kinase C

• Protein kinase C - Activates myosin light-chain phosphorylation granule movements that disassemble the actin-myosin complexes

• Rab-associated kinases and phosphatases - Regulate cell granule membrane fusion in resting mast cells

Histamine Intolerance

Histamine dilates post-capillary venules, activates the endothelium, and increases blood vessel permeability. This leads to local edema, warmth, redness, and the attraction of other inflammatory cells to the site of release.  R

The first responders of the immune system to injury of the CNS, or central nervous system, are brain mast cells. Even before microglia. R

Mast cells hang out by blood vessels and discharge cytokines. This response activates microglia. R

Mast cell activation activates microglia and therefore causes neuroinflammation. R

Mastocytosis is caused by the presensce of too many mast cells and CD34+ mast cell precursors. R

Symptoms

When too many mast cells exist in a person's body and undergo degranulation. The additional chemicals can cause a number of symptoms which can vary over time and can range in intensity from mild to severe. The symptoms of mastocytosis often are similar to the symptoms of an allergic reaction: R

• Fatigue

• Skin lesions (urticaria pigmentosa), itching, and dermatographic urticaria (skin writing)

• Abdominal discomfort

• Nausea and vomiting

• Diarrhea

• Olfactive intolerance

• Infections (bronchitis, rhinitis, and conjunctivitis)

• Ear/nose/throat inflammation

• Anaphylaxis (shock from allergic or immune causes)

• Episodes of very low blood pressure (including shock) and faintness

• Bone or muscle pain

• Decreased bone density or increased bone density (osteoporosis or osteosclerosis)

• Headache

• Depression R

• Ocular discomfort

• Increased stomach acid production causing peptic ulcers (increased stimulation of enterochromaffin cell and direct histamine stimulation on parietal cell)

• Malabsorption (due to inactivation of pancreatic enzymes by increased acid) R

Autism

Most ASD (Autism Spectrum Disorder) patients have food intolerance and other allergic symptomatology indicative of mast cell activation. Allergic, infectious, neuroimmune and environmental triggers may activate mast cells to release vasoactive, inflammatory and neurotoxic molecules. These could disrupt the gut-blood-brain-barriers and/or activate susceptibility genes, thus contributing to brain inflammation and ASD. R

MCAD, or MCAS, is where mast cells inappropriately and excessively release chemical mediators, resulting in chronic symptoms.R R R

Unlike mastocytosis, where patients have an abnormally increased number of mast cells, patients with MCAD have a normal number of mast cells that do not function properly and are defined as "hyperresponsive." R

Symptoms

Many signs and symptoms are the same as those for Mastocytosis, because both conditions result in too many mediators released by mast cells. R

• Dermatological - flushing, easy bruising, either a reddish or a pale complexion, itchiness

• Cardiovascular - lightheadedness, dizziness, presyncope, syncope

• Gastrointestinal - diarrhea, cramping, intestinal discomfort, nausea, vomitting

• Psychological & Neurological - brain fog, short term memory dysfunction, difficulty with recalling words, headaches, migraines

• Respiratory - congestion, coughing, wheezing

• Vision/Eyes - ocular discomfort, conjunctivitis

• Constitutional - general fatigue and malaise, food, drug, and chemical/fragrance intolerances, sense of being cold all the time

• Musculoskeletal - osteoporosis and osteopenia

• Anaphylaxis

Triggers

• Foods high in histamine R

• temperature extremes R

• airborne smells including perfumes or smokeR

• exercise or exertion R

• emotional stress R

• hormonal changes (adolescence, pregnancy, menstrual cycles) R

Histamine Intolerance

See all tests for histamine Intolerance.

Mastocytosis

• Skin Biopsy

• Serum tryptase

• Histamine

MCAD

• N-methyl histamine

• prostaglandin D2

• beta- prostaglandin F2 alpha

• leukotriene E4

• Histamine

All of these tests can be ordered here 

I take Brain Gain to stabilize mast cells and clear brain fog.

• Cannabinoids CB1 and CB2 R

• Vitamin D3 R

• Cinnamon R

• Quercitin R

• Luteolin R

• Diosmetin R

• Apigenin R

• Fisetin R

• Kaempferol R

• Ginkgetin R

• EGCG R

• Silymarin R

• Scopletin R R

• Zinc R

• Scarporone R

• Artekeiskeanol A RR

• Selinidin R

• 5-Methoxy-8-(2-hydroxy-3-butoxy-3-methylbutyloxy)-psoralen R

• Cinnamic Acid R

• Ellagic Acid R

• Magnolol and Honokiol R

• Resveratrol R

• Polydatin R

• Curcumin R

• Mangostin-α, -β and -γ R

• Parthenolide R

• Sesquiterpene Lactones (SQLTs) R

• Monoterpenes R

• Palmitoylethanolamide (PEA) R

• Sinomenine R

• Indoline R

• Xestopongin C R

• Theanine R

• Pemirolast R

• Omalizumab R

• Olopatadine R

• Xanthine R

• Ketotifen R

• Cromoglicic Acid R

• β2 adrenergic receptor agonists R

• 2-Hydroxy-3-methoxybenzoic acid R

See upcoming interview with Dr. Theoharides PhD MD.