Жаңаш клеткасы: Қолқа шекаралық тініндегі қызметі мен қасиеттері

Cell found in connective tissue

A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumors.

Mast cells are very similar to basophil granulocytes (a class of white blood cells) in blood, in the sense that both are granulated cells that contain histamine and heparin, an anticoagulant. Their nuclei differ in that the basophil nucleus is lobated while the mast cell nucleus is round. The Fc region of immunoglobulin E (IgE) becomes bound to mast cells and basophils, and when IgE's paratopes bind to an antigen, it causes the cells to release histamine and other inflammatory mediators. These similarities have led many to speculate that mast cells are basophils that have "homed in" on tissues. Furthermore, they share a common precursor in bone marrow expressing the CD34 molecule. Basophils leave the bone marrow already mature, whereas the mast cell circulates in an immature form, only maturing once in a tissue site. The site an immature mast cell settles in probably determines its precise characteristics. The first in vitro differentiation and growth of a pure population of mouse mast cells has been carried out using conditioned medium derived from concanavalin A stimulated splenocytes. Later, it was discovered that T cell derived interleukin 3 was the component present in the conditioned media that was required for mast cell differentiation and growth. Mast cells in rodents are classically divided into two subtypes: connective tissue type mast cells and mucosal mast cells. The activities of the latter are dependent on T cells. Mast cells are present in most tissues characteristically surrounding blood vessels, nerves and lymphatic vessels, and are especially prominent near the boundaries between the outside world and the internal milieu, such as the skin, mucosa of the lungs, and digestive tract, as well as the mouth, conjunctiva, and nose. In general, allergens are proteins or polysaccharides. The allergen binds to the antigen binding sites, which are situated on the variable regions of the IgE molecules bound to the mast cell surface. It appears that binding of two or more IgE molecules (cross linking) is required to activate the mast cell. 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. Although this reaction is most well understood in terms of allergy, it appears to have evolved as a defense system against parasites and bacteria.

Unlike other hematopoietic cells of the immune system, mast cells naturally occur in the human brain where they interact with the neuroimmune system. In the brain, mast cells are located in a number of structures that mediate visceral sensory (e. g. pain) or neuroendocrine functions or that are located along the blood–cerebrospinal fluid barrier, including the pituitary stalk, pineal gland, thalamus, and hypothalamus, area postrema, choroid plexus, and in the dural layer of the meninges near meningeal nociceptors. Across systems, mast cells serve as the main effector cell through which pathogens can affect the gut–brain axis. When these mast cells initially degranulate, they release mediators (e. g., histamine, tryptase, and serotonin) which activate, sensitize, and upregulate membrane expression of nociceptors (i. e., TRPV1) on visceral afferent neurons via their receptors (respectively, HRH1, HRH2, HRH3, PAR2, 5 HT3);

FcεR1 is a high affinity IgE receptor that is expressed on the surface of the mast cell. FcεR1 is a tetramer made of one alpha (α) chain, one beta (β) chain, and two identical, disulfide linked gamma (γ) chains. The binding site for IgE is formed by the extracellular portion of the α chain that contains two domains that are similar to Ig. One transmembrane domain contains an aspartic acid residue, and one contains a short cytoplasmic tail. The β chain contains, a single immunoreceptor tyrosine based activation motif ITAM, in the cytoplasmic region. Each γ chain has one ITAM on the cytoplasmic region. The signaling cascade from the receptor is initiated when the ITAMs of the β and γ chains are phosphorylated by a tyrosine kinase. This signal is required for the activation of mast cells. Type 2 helper T cells,(Th2) and many other cell types lack the β chain, so signaling is mediated only by the γ chain. This is due to the α chain containing endoplasmic reticulum retention signals that causes the α chains to remain degraded in the ER. The assembly of the α chain with the co transfected β and γ chains mask the ER retention and allows the α β γ complex to be exported to the golgi apparatus to the plasma membrane in rats. In humans, only the γ complex is needed to counterbalance the α chain ER retention. This antigen stimulated phosphorylation causes the activation of other proteins in the FcεR1 mediated signaling cascade.

An important adaptor protein activated by the Syk phosphorylation step is the linker for activation of T cells (LAT). LAT can be modified by phosphorylation to create novel binding sites. This leads to signal transduction to a G protein and activation of the mast cell. Mast cell activation induces the release of antibacterial mediators including ROS, TNF α and PRGD2 which institute the recruitment of other immune cells to inhibit bacterial growth and biofilm formation. The MRGPRX2 receptor is a possible therapeutic target and can be pharmacologically activated using the agonist compound 48/80 to control bacterial infection. It is also hypothesised that other QSMs and even Gram negative bacterial signals can activate this receptor. This might particularly be the case during Bartonella chronic infections where it appears clearly in human symptomatology that these patients all have a mast cell activation syndrome due to the presence of a not yet defined quorum sensing molecule (basal histamine itself?). Those patients are prone to food intolerance driven by another less specific path than the IgE receptor path: certainly the MRGPRX2 route. These patients also show cyclical skin pathergy and dermographism, every time the bacteria exits its hidden intracellular location.

Enzyme Function 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 GAB2 GAB2 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

Mast cells are activated in response to infection by pathogenic parasites, such as certain helminths and protozoa, through IgE signaling.

Mast cell activation disorders (MCAD) are a spectrum of immune disorders that are unrelated to pathogenic infection and involve similar symptoms that arise from secreted mast cell intermediates, but differ slightly in their pathophysiology, treatment approach, and distinguishing symptoms. The classification of mast cell activation disorders was laid out in 2010. Many forms of cutaneous and mucosal allergy are mediated in large part by mast cells; they play a central role in asthma, eczema, itch (from various causes), allergic rhinitis and allergic conjunctivitis. Antihistamine drugs act by blocking histamine action on nerve endings. Cromoglicate based drugs (sodium cromoglicate, nedocromil) block a calcium channel essential for mast cell degranulation, stabilizing the cell and preventing release of histamine and related mediators. Leukotriene antagonists (such as montelukast and zafirlukast) block the action of leukotriene mediators and are being used increasingly in allergic diseases. Vasodilation and increased permeability of capillaries are a result of both H1 and H2 receptor types. Stimulation of histamine activates a histamine (H2) sensitive adenylate cyclase of oxyntic cells, and there is a rapid increase in cellular [cAMP] that is involved in activation of H+ transport and other associated changes of oxyntic cells.

In anaphylaxis (a severe systemic reaction to allergens, such as nuts, bee stings, or drugs), the body wide degranulation of mast cells leads to vasodilation and, if severe, symptoms of life threatening shock. Histamine is a vasodilatory substance released during anaphylaxis.

Mastocytosis is a rare clonal mast cell disorder involving the presence of too many mast cells (mastocytes) and CD34+ mast cell precursors. Mutations in c Kit are associated with mastocytosis. Other neoplastic disorders associated with mast cells include mast cell sarcoma and mast cell leukemia.

Mast cell activation syndrome (MCAS) is an idiopathic immune disorder that involves recurrent and excessive mast cell degranulation and which produces symptoms that are similar to other mast cell activation disorders. They are now considered to be part of the immune system.

Research into an immunological contribution to autism suggests that autism spectrum disorder (ASD) children may present with "allergic like" problems in the absence of elevated serum IgE and chronic urticaria, suggesting non allergic mast cell activation in response to environmental and stress triggers. This mast cell activation could contribute to brain inflammation and neurodevelopmental problems.

Toluidine blue: one of the most common stains for acid mucopolysaccharides and glycoaminoglycans, components of mast cells granules. Bismarck brown: stains mast cell granules brown. Surface markers: cell surface markers of mast cells were discussed in detail by Heneberg, claiming that mast cells may be inadvertently included in the stem or progenitor cell isolates, since part of them is positive for the CD34 antigen. The classical mast cell markers include the high affinity IgE receptor, CD117 (c Kit), and CD203c (for most of the mast cell populations). Expression of some molecules may change in course of the mast cell activation.

Mast cells and enterochromaffin cells are the source of most serotonin in the stomach in rodents.