Target type: biologicalprocess
Any process that activates or increases the frequency, rate, or extent of mast cell activation as part of an immune response. [GOC:mah]
Positive regulation of mast cell activation involved in immune response is a complex biological process that plays a crucial role in initiating and modulating immune responses. Mast cells are resident immune cells found in connective tissues throughout the body, particularly near blood vessels and mucosal surfaces. They are highly specialized cells that possess a large number of granules containing various pre-formed mediators, including histamine, proteases, and cytokines. Upon activation, mast cells release these mediators, which can trigger a wide range of physiological effects, including vasodilation, bronchoconstriction, and inflammation.
The activation of mast cells is tightly regulated by a variety of factors, including allergens, pathogens, and cytokines. These stimuli trigger signaling pathways within the mast cell, ultimately leading to the release of inflammatory mediators. The process of positive regulation of mast cell activation involves a series of molecular events that amplify and enhance the activation signal, leading to a robust and sustained response.
One key pathway involved in positive regulation of mast cell activation is the FcεRI signaling pathway. FcεRI is a high-affinity receptor for IgE, an antibody that plays a crucial role in allergic reactions. When IgE binds to FcεRI on the mast cell surface, it cross-links the receptor, triggering a cascade of intracellular signaling events. This cross-linking activates various signaling molecules, including tyrosine kinases, phospholipases, and transcription factors. The activation of these signaling molecules leads to the release of calcium from intracellular stores, the activation of protein kinases, and the production of second messengers, such as diacylglycerol (DAG) and inositol trisphosphate (IP3).
DAG and IP3 activate downstream signaling pathways that ultimately lead to the release of inflammatory mediators from mast cell granules. DAG activates protein kinase C (PKC), which phosphorylates and activates other signaling proteins, including those involved in granule exocytosis. IP3 triggers the release of calcium from intracellular stores, which is essential for the fusion of granules with the cell membrane and the subsequent release of their contents.
In addition to FcεRI signaling, other pathways can also contribute to the positive regulation of mast cell activation. For example, mast cells can be activated by complement components, such as C5a, and by cytokines, such as TNF-alpha and IL-1. These stimuli trigger different signaling pathways that converge on common downstream targets, leading to the amplification and enhancement of the activation signal.
The positive regulation of mast cell activation is essential for the development of effective immune responses. By amplifying the activation signal, mast cells can rapidly release a large amount of inflammatory mediators, which can effectively recruit and activate other immune cells, such as neutrophils, eosinophils, and macrophages. These cells contribute to the containment and clearance of pathogens and the repair of damaged tissues.
However, dysregulation of mast cell activation can lead to the development of various inflammatory and allergic diseases. For example, in allergic reactions, excessive activation of mast cells by allergens triggers the release of histamine and other inflammatory mediators, leading to symptoms such as sneezing, coughing, and skin rashes. In other diseases, such as asthma and chronic urticaria, mast cells are thought to play a role in the development and progression of disease.
Therefore, understanding the mechanisms underlying the positive regulation of mast cell activation is crucial for the development of novel therapeutic strategies for treating inflammatory and allergic diseases. By targeting specific signaling pathways or molecules involved in mast cell activation, it may be possible to modulate the inflammatory response and improve patient outcomes.'
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Protein | Definition | Taxonomy |
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Sphingosine kinase 2 | A sphingosine kinase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NRA0] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
fingolimod hydrochloride | fingolimod hydrochloride : The hydrochloride salt of 2-amino-2-[2-(4-octylphenyl) ethyl]-1,3-propanediol (fingolimod). Fingolimod Hydrochloride: A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS. | hydrochloride | immunosuppressive agent; prodrug; sphingosine-1-phosphate receptor agonist |
4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol | substituted aniline | ||
sphingosine | 2-aminooctadec-4-ene-1,3-diol : A 2-aminooctadecene-1,3-diol having its double bond at position 4. sphing-4-enine : A sphingenine in which the C=C double bond is located at the 4-position. sphingenine : A 2-aminooctadecene-1,3-diol having (2S,3R)-configuration. sphingoid : Sphinganine, its homologs and stereoisomers, and the hydroxy and unsaturated derivatives of these compounds. | sphing-4-enine | human metabolite; mouse metabolite |
n,n-dimethylsphingenine | N,N-dimethylsphingosine : A sphingoid that is sphingosine in which the two amino hydrogens are replaced by methyl groups. N,N-dimethylsphingosine: a sphingosine kinase inhibitor | aminodiol; sphingoid; tertiary amino compound | EC 2.7.1.91 (sphingosine kinase) inhibitor; metabolite |
es-285 | 1-deoxysphinganine : A bioactive sphingoid, sphinganine, in which the terminal hydroxy group has been replaced by a hydrogen. spisulosine: from marine organism, Spisula polynyma; structure in first source | amino alcohol; sphingoid | antineoplastic agent |
3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide | organochlorine compound | ||
bml 258 | |||
pf-543 | PF-543: Sphingosine Kinase 1 Selective Inhibitor; structure in first source | sulfonamide | |
rome | (2R)-2-amino-2-(methoxymethyl)-4-(4-octylphenyl)butan-1-ol : A 2-amino-2-(methoxymethyl)-4-(4-octylphenyl)butan-1-ol that has R-configuration. It is a sphingosine kinase-2 inhibitor. Rome: The capital city of Italy. | 2-amino-2-(methoxymethyl)-4-(4-octylphenyl)butan-1-ol | EC 2.7.1.91 (sphingosine kinase) inhibitor |