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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Protein | Definition | Taxonomy |
---|---|---|
Mas-related G-protein coupled receptor member X2 | A Mas-related G-protein coupled receptor X2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q96LB1] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
methadone | 6-(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 | |
dextropropoxyphene | dextropropoxyphene : 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 propanoate | mu-opioid receptor agonist; opioid analgesic |
substance p | peptide | neurokinin-1 receptor agonist; neurotransmitter; vasodilator agent | |
metazocine | metazocine: more than 13 isomers available; structure given in first source | benzazocine | |
codeine | morphinane alkaloid; organic heteropentacyclic compound | antitussive; drug allergen; environmental contaminant; opioid analgesic; opioid receptor agonist; prodrug; xenobiotic | |
hydrocodone | hydrocodone : 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 |
morphine | Meconium: 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-neoendorphin | alpha-neoendorphin: precursor or leucine enkephalin family | ||
thebaine | Thebaine: 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 | |
levorphanol | Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. | morphinane alkaloid | |
morphine-6-glucuronide | morphine-6-glucuronide: RN given refers to (5alpha,6alpha)-isomer | morphinane alkaloid | |
sinomenine | sinomenine: isolated from root of Sinomenium acutum; antirheumatic, antineuralgic | morphinane alkaloid | |
6-o-monoacetylmorphine | 6-O-monoacetylmorphine: RN given refers to parent cpd(5alpha,6alpha)-isomer | morphinane alkaloid | |
morphine-3-glucuronide | morphine-3-glucuronide: RN given refers to (5alpha,6alpha)-isomer | morphinane alkaloid | |
acetylcodeine | |||
codeine-6-glucuronide | codeine-6-glucuronide: structure given in first source | morphinane alkaloid | |
norcodeine | norcodeine : 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 67 | quinolines | ||
adl 5859 | |||
dynorphins | Dynorphins: 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 14 | cortistatin: 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 | |||
dynorphins | dynorphin (1-13): potent opioid peptide; see also record for dynorphin & D-Ala(2)-dynorphin (1-11) |