Page last updated: 2024-10-24

mast cell activation

Definition

Target type: biologicalprocess

The change in morphology and behavior of a mast cell resulting from exposure to a cytokine, chemokine, soluble factor, or to (at least in mammals) an antigen which the mast cell has specifically bound via IgE bound to Fc-epsilonRI receptors. [GOC:mgi_curators, ISBN:0781735149]

Mast cell activation is a complex process that involves the recognition of specific stimuli by receptors on the surface of mast cells, followed by a cascade of intracellular signaling events that ultimately lead to the release of a variety of potent mediators. These mediators can contribute to a wide range of physiological and pathological processes, including inflammation, allergy, and immunity.

**Stimuli that Trigger Mast Cell Activation**

Mast cells are highly sensitive to a variety of stimuli, including:

- **Immunoglobulin E (IgE):** IgE is an antibody that is produced by B cells and binds to FcεRI receptors on the surface of mast cells. When IgE binds to its receptor and is subsequently cross-linked by an allergen, this triggers the release of mast cell mediators. This is the mechanism involved in allergic reactions.

- **Complement proteins:** Certain complement proteins, such as C5a, can directly activate mast cells.

- **Cytokines:** Interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and other cytokines can also activate mast cells.

- **Physical stimuli:** Mechanical injury, heat, and cold can also trigger mast cell activation.

- **Neurotransmitters:** Neurotransmitters such as substance P can stimulate mast cell activation.

**Intracellular Signaling Pathways**

Once a stimulus is recognized, it initiates a series of intracellular signaling events. These events involve:

- **Tyrosine kinase signaling:** The FcεRI receptor, upon cross-linking, triggers the activation of tyrosine kinases such as Lyn and Syk.

- **Calcium signaling:** Tyrosine kinases activate phospholipase Cγ (PLCγ), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 increases intracellular calcium levels, which triggers the release of preformed mediators from granules.

- **Activation of transcription factors:** DAG activates protein kinase C (PKC), which in turn phosphorylates and activates transcription factors such as nuclear factor κB (NF-κB) and activator protein-1 (AP-1). These transcription factors regulate the expression of genes encoding for newly synthesized mediators.

**Mediators Released by Mast Cells**

Mast cells release a wide range of mediators, including:

- **Preformed mediators:**
- **Histamine:** A potent vasodilator and bronchoconstrictor.
- **Heparin:** An anticoagulant.
- **Proteases:** Enzymes that degrade proteins.
- **Chemotactic factors:** Molecules that attract other immune cells to the site of inflammation.

- **Newly synthesized mediators:**
- **Leukotrienes:** Proinflammatory lipid mediators that cause bronchoconstriction and smooth muscle contraction.
- **Prostaglandins:** Lipid mediators that contribute to inflammation and pain.
- **Cytokines:** Signaling molecules that regulate immune responses.

**Functions of Mast Cell Activation**

Mast cell activation plays a crucial role in:

- **Immune defense:** Mast cells participate in the innate immune response against parasites and bacterial infections.

- **Inflammation:** Mast cell mediators contribute to the development of inflammatory responses.

- **Allergy:** Mast cell activation is the key event in allergic reactions, leading to symptoms such as sneezing, runny nose, and difficulty breathing.

- **Wound healing:** Mast cells promote wound healing by releasing growth factors and other mediators.

- **Tissue remodeling:** Mast cells contribute to tissue remodeling in response to injury or infection.

**Dysregulation of Mast Cell Activation**

Excessive or inappropriate mast cell activation can contribute to a variety of pathological conditions, including:

- **Allergic diseases:** Asthma, hay fever, and food allergies.

- **Autoimmune diseases:** Rheumatoid arthritis, systemic lupus erythematosus.

- **Inflammatory bowel disease:** Crohn's disease, ulcerative colitis.

- **Chronic urticaria:** A skin condition characterized by itchy welts.

- **Mastocytosis:** A rare condition characterized by an overgrowth of mast cells.

**Conclusion**

Mast cell activation is a highly regulated process that plays a critical role in both health and disease. Understanding the mechanisms of mast cell activation is essential for developing new therapeutic strategies for a wide range of conditions.'
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Proteins (1)

ProteinDefinitionTaxonomy
Mas-related G-protein coupled receptor member X2A Mas-related G-protein coupled receptor X2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q96LB1]Homo sapiens (human)

Compounds (23)

CompoundDefinitionClassesRoles
methadone6-(dimethylamino)-4,4-diphenylheptan-3-one : A ketone that is heptan-3-one substituted by a dimethylamino group at position 6 and two phenyl groups at position 4.

methadone : A racemate comprising equimolar amounts of dextromethadone and levomethadone. It is a opioid analgesic which is used as a painkiller and as a substitute for heroin in the treatment of heroin addiction.

Methadone: A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)
benzenes;
diarylmethane;
ketone;
tertiary amino compound
dextropropoxyphenedextropropoxyphene : The (1S,2R)-(+)-diastereoisomer of propoxyphene.

Dextropropoxyphene: A narcotic analgesic structurally related to METHADONE. Only the dextro-isomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect.

propoxyphene : A racemate of the (1R,2R)- and (1S,2R)- diastereoisomers.
1-benzyl-3-(dimethylamino)-2-methyl-1-phenylpropyl propanoatemu-opioid receptor agonist;
opioid analgesic
substance ppeptideneurokinin-1 receptor agonist;
neurotransmitter;
vasodilator agent
metazocinemetazocine: more than 13 isomers available; structure given in first sourcebenzazocine
codeinemorphinane alkaloid;
organic heteropentacyclic compound
antitussive;
drug allergen;
environmental contaminant;
opioid analgesic;
opioid receptor agonist;
prodrug;
xenobiotic
hydrocodonehydrocodone : A morphinane-like compound that is a semi-synthetic opioid synthesized from codeine.

Hydrocodone: Narcotic analgesic related to CODEINE, but more potent and more addicting by weight. It is used also as cough suppressant.
morphinane-like compound;
organic heteropentacyclic compound
antitussive;
mu-opioid receptor agonist;
opioid analgesic
morphineMeconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.morphinane alkaloid;
organic heteropentacyclic compound;
tertiary amino compound
anaesthetic;
drug allergen;
environmental contaminant;
geroprotector;
mu-opioid receptor agonist;
opioid analgesic;
plant metabolite;
vasodilator agent;
xenobiotic
alpha-neoendorphinalpha-neoendorphin: precursor or leucine enkephalin family
thebaineThebaine: A drug that is derived from opium, which contains from 0.3-1.5% thebaine depending on its origin. It produces strychnine-like convulsions rather than narcosis. It may be habit-forming and is a controlled substance (opiate) listed in the U.S. Code of Federal Regulations, Title 21 Part 1308.12 (1985). (From Merck Index, 11th ed)morphinane alkaloid;
organic heteropentacyclic compound
levorphanolLevorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection.morphinane alkaloid
morphine-6-glucuronidemorphine-6-glucuronide: RN given refers to (5alpha,6alpha)-isomermorphinane alkaloid
sinomeninesinomenine: isolated from root of Sinomenium acutum; antirheumatic, antineuralgicmorphinane alkaloid
6-o-monoacetylmorphine6-O-monoacetylmorphine: RN given refers to parent cpd(5alpha,6alpha)-isomermorphinane alkaloid
morphine-3-glucuronidemorphine-3-glucuronide: RN given refers to (5alpha,6alpha)-isomermorphinane alkaloid
acetylcodeine
codeine-6-glucuronidecodeine-6-glucuronide: structure given in first sourcemorphinane alkaloid
norcodeinenorcodeine : A morphinane-like compound that is the N-demethylated derivative of codeine.

norcodeine: RN given refers to (5 alpha,6 alpha)-isomer
morphinane alkaloid
tan 67quinolines
adl 5859
dynorphinsDynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.
cortistatin 14cortistatin: a cortical neuropeptide; shows strong structural similarity to somatostatin; a neuronal depressant; has sleep-modulating activity; amino acid sequence given in first source
bam 22p
dynorphinsdynorphin (1-13): potent opioid peptide; see also record for dynorphin & D-Ala(2)-dynorphin (1-11)