The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.
Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.
A potent mast cell degranulator. It is involved in histamine release.
The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects.
An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.
An evanescent cutaneous reaction occurring when antibody is injected into a local area on the skin and antigen is subsequently injected intravenously along with a dye. The dye makes the rapidly occurring capillary dilatation and increased vascular permeability readily visible by leakage into the reaction site. PCA is a sensitive reaction for detecting very small quantities of antibodies and is also a method for studying the mechanisms of immediate hypersensitivity.
Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).
An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
A hexosaminidase specific for non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. It acts on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES. Two specific mammalian isoenzymes of beta-N-acetylhexoaminidase are referred to as HEXOSAMINIDASE A and HEXOSAMINIDASE B. Deficiency of the type A isoenzyme causes TAY-SACHS DISEASE, while deficiency of both A and B isozymes causes SANDHOFF DISEASE. The enzyme has also been used as a tumor marker to distinguish between malignant and benign disease.
A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.
Condensed areas of cellular material that may be bounded by a membrane.
An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.
A family of neutral serine proteases with TRYPSIN-like activity. Tryptases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.
A cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis.
Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)
Norbornanes are a class of bicyclic organic compounds consisting of a hydrocarbon skeleton made up of two fused 5-membered rings, where five of the six ring carbons are bonded to hydrogens and one is bonded to two additional carbon atoms, forming a bridge between the rings.
Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes.
An in vitro test used in the diagnosis of allergies including drug hypersensitivity. The allergen is added to the patient's white blood cells and the subsequent histamine release is measured.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.
A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.
A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.
Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress.
Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.
The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.
Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.
A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.
A family of soil bacteria. It also includes some parasitic forms.
The minute vessels that collect blood from the capillary plexuses and join together to form veins.
A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GQ and the subsequently activates TYPE C PHOSPHOLIPASES. Additional evidence has shown that the receptor can act through a calcium-dependent signaling pathway.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
Conjunctivitis due to hypersensitivity to various allergens.
A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI and subsequently inhibits ADENYLYL CYCLASES.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.
Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Any inflammation of the skin.
Substances that are recognized by the immune system and induce an immune reaction.
Antibodies, especially IGE, that bind to tissue of the same species so that ANTIGENS induce release of HISTAMINE and other vasoactive agents. HYPERSENSITIVITY is the clinical manifestation.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A heterogenous group of disorders characterized by the abnormal increase of MAST CELLS in only the skin (MASTOCYTOSIS, CUTANEOUS), in extracutaneous tissues involving multiple organs (MASTOCYTOSIS, SYSTEMIC), or in solid tumors (MASTOCYTOMA).
A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity.
Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cell surface proteins that bind neurotensin with high affinity and trigger intracellular changes which influence the behavior of cells. Neurotensin and neurotensin receptors are found in the central nervous system and in the periphery.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the STOMACH. The two sacs are connected by the foramen of Winslow, or epiploic foramen.
An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. In PLATELETS and T-LYMPHOCYTES it may play a role in the cellular degranulation process.
Inbreed BN (Brown Norway) rats are a strain of laboratory rats that are specifically bred for research purposes, characterized by their uniform genetic makeup and susceptibility to various diseases, which makes them ideal models for studying human physiology and pathophysiology.
A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.
A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.
The circulation of blood through the BLOOD VESSELS supplying the abdominal VISCERA.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Established cell cultures that have the potential to propagate indefinitely.
Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.
A rare acute myeloid leukemia in which the primary differentiation is to BASOPHILS. It is characterized by an extreme increase of immature basophilic granulated cells in the bone marrow and blood. Mature basophils are usually sparse.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Mice bearing mutant genes which are phenotypically expressed in the animals.
Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.
Elements of limited time intervals, contributing to particular results or situations.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
Adherence of cells to surfaces or to other cells.
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.
Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.
The relationship between the dose of an administered drug and the response of the organism to the drug.

Borrelia burgdorferi spirochetes induce mast cell activation and cytokine release. (1/1340)

The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-alpha release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-alpha-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells.  (+info)

Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of corticotropin-releasing hormone receptors. (2/1340)

Urocortin (Ucn) is related to corticotropin-releasing hormone (CRH), and both are released in the brain under stress where they stimulate CRH 1 and 2 receptors (CRHR). Outside the brain, they may have proinflammatory actions through activation of mast cells, which are located perivascularly close to nerve endings and degranulate in response to acute psychological stress. Here, we report that a concentration of intradermal Ucn as low as 10 nM induced dose-dependent rat skin mast cell degranulation and increased vascular permeability. This effect appeared to be equipotent to that of calcitonin gene-related peptide and neurotensin. Ucn-induced skin vasodilation was inhibited by pretreatment with the mast cell stabilizer disodium cromoglycate (cromolyn) and was absent in the mast cell-deficient W/Wv mice. The selective nonpeptide CRH receptor 1 antagonist, antalarmin and the nonselective peptide antagonist astressin both reduced vascular permeability triggered by Ucn but not that by Substance P or histamine. In contrast, the peptide antagonist alpha-helical CRH-(9-41) reduced the effect of all three. The vasodilatory effect of Ucn was largely inhibited by pretreatment with H1 receptor antagonists, suggesting that histamine is the major mediator involved in vitro. Neuropeptide depletion of sensory neurons, treatment with the ganglionic blocker hexamethonium, or in situ skin infiltration with the local anesthetic lidocaine did not affect Ucn-induced vascular permeability, indicating that its in situ effect was not mediated through the peripheral nervous system. These results indicate that Ucn is one of the most potent triggers of rat mast cell degranulation and skin vascular permeability. This effect of Ucn may explain stress-induced disorders, such as atopic dermatitis or psoriasis, and may lead to new forms of treatment.  (+info)

A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation. (3/1340)

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that is widely used to treat neutropenia. In addition to stimulating polymorphonuclear neutrophil (PMN) production, G-CSF may have significant effects on PMN function. Because G-CSF receptor (G-CSFR)-deficient mice do not have the expected neutrophilia after administration of human interleukin-8 (IL-8), we examined the effect of the loss of G-CSFR on IL-8-stimulated PMN function. Compared with wild-type PMNs, PMNs isolated from G-CSFR-deficient mice demonstrated markedly decreased chemotaxis to IL-8. PMN emigration into the skin of G-CSFR-deficient mice in response to IL-8 was also impaired. Significant chemotaxis defects were also seen in response to N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, or macrophage inflammatory protein-2. The defective chemotactic response to IL-8 does not appear to be due to impaired chemoattractant receptor function, as the number of IL-8 receptors and chemoattractant-induced calcium influx, actin polymerization, and release of gelatinase B were comparable to those of wild-type PMNs. Chemoattractant-induced adhesion of G-CSFR-deficient PMNs was significantly impaired, suggesting a defect in beta2-integrin activation. Collectively, these data demonstrate that selective defects in PMN activation are present in G-CSFR-deficient mice and indicate that G-CSF plays an important role in regulating PMN chemokine responsiveness.  (+info)

Neurotensin is a proinflammatory neuropeptide in colonic inflammation. (4/1340)

The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous colitis in humans. In animal models, toxin A causes an acute inflammatory response characterized by activation of sensory neurons and intestinal nerves and immune cells of the lamina propria. Here we show that neurotensin and its receptor are elevated in the rat colonic mucosa following toxin A administration. Pretreatment of rats with the neurotensin receptor antagonist SR-48, 692 inhibits toxin A-induced changes in colonic secretion, mucosal permeability, and histologic damage. Exposure of colonic explants to toxin A or neurotensin causes mast cell degranulation, which is inhibited by SR-48,692. Because substance P was previously shown to mediate mast cell activation, we examined whether substance P is involved in neurotensin-induced mast cell degranulation. Our results show that neurotensin-induced mast cell degranulation in colonic explants is inhibited by the substance P (neurokinin-1) receptor antagonist CP-96,345, indicating that colonic mast activation in response to neurotensin involves release of substance P. We conclude that neurotensin plays a key role in the pathogenesis of C. difficile-induced colonic inflammation and mast cell activation.  (+info)

Mucosal mast cell secretion processes imaged using three-photon microscopy of 5-hydroxytryptamine autofluorescence. (5/1340)

The secretion process of the mucosal mast cell line RBL-2H3 was imaged using infrared three photon excitation (3PE) of serotonin (5-hydroxytryptamine, 5-HT) autofluorescence, a measurement previously difficult because of the technical intractability of deep UV optics. Images of prestimulation 5-HT distributions were analyzed in loaded cell populations (those incubated in a 5-HT-rich medium overnight) and in unloaded populations and were found to be strictly quantifiable by comparison with bulk population high-performance liquid chromatography measurements. Antigenically stimulated cells were observed to characteristically ruffle and spread as granular 5-HT disappeared with no detectable granule movement. Individual cells exhibited highly heterogeneous release kinetics, often with quasi-periodic bursts. Neighboring granule disappearances were correlated, indicative of either spatially localized signaling or granule-granule interactions. In one-half of the granule release events, weak residual fluorescence was visible suggestive of leftover 5-HT still bound to the granule matrix. The terminal stages of secretion (>300 s) consisted primarily of unresolved granules and remainder 5-HT leakage from already released granules.  (+info)

Tracking single secretory granules in live chromaffin cells by evanescent-field fluorescence microscopy. (6/1340)

We have observed secretory granules beneath the plasma membrane of chromaffin cells. Using evanescent-field excitation by epiillumination, we have illuminated a thin layer of cytosol where cells adhere to glass coverslips. Up to 600 frames could be recorded at diffraction-limited resolution without appreciable photodynamic damage. We localized single granules with an uncertainty of approximately 30 nm and tracked their motion in three dimensions. Granules in resting cells wander randomly as if imprisoned in a cage that leaves approximately 70 nm space around a granule. The "cage" itself moves only slowly (D = 2 x 10(-12) cm2/s). Rarely do granules arrive at or depart from the plasma membrane of resting cells. Stimulation increases lateral motion only slightly. After the plasma membrane has been depleted of granules by exocytosis, fresh granules can be seen to approach it at an angle. The method will be useful for exploring the molecular steps preceding exocytosis at the level of single granules.  (+info)

LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. (7/1340)

The eicosanoid lipoxin A4 (LXA4) is biosynthesized in vivo by cells present at inflammatory sites and appears to be an endogenous anti-inflammatory mediator. Further, in the presence of aspirin, the 15-epimer of LXA4 (15-epi-LXA4) is biosynthesized and may mediate some of aspirin's desirable bioactions. LXA4, 15-epi-LXA4, and their stable analogs inhibit inflammation in established animal models, indicating that these compounds may be useful for treating inflammatory disease states. To investigate the cellular mechanisms by which these lipid mediators downregulate inflammation, we investigated whether these eicosanoids could influence receptor-mediated degranulation of human neutrophils, an event thought to play a major causative role in several inflammatory disease states. LXA4, 15-epi-LXA4, and their stable analogs potently (IC50 < 1 nM) and selectively downregulated neutrophil release of azurophilic granule contents but did not affect other neutrophil secretory functions. Thus the cellular basis of action of these natural off-switches to inflammation appears to involve downregulation of neutrophil azurophilic granule release.  (+info)

Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. (8/1340)

Nerve growth factor (NGF) is well recognized to have a number of potent effects on mast cells, including increasing mast cell numbers in vivo and inducing mast cell degranulation in vitro. More recently, NGF has been demonstrated to induce PGD2 production by mast cells through the induction of mast cell cyclooxygenase expression. We have observed that NGF at doses as low as 10 ng/ml will induce IL-6 production and inhibit TNF-alpha release from rat peritoneal mast cells in the presence of lysophosphatidylserine as a cofactor. NGF synergizes with LPS treatment of peritoneal mast cells (PMC) for the induction of IL-6. Examination of the mechanism of this phenomenon has revealed that NGF can induce both rat PMC and mouse bone marrow-derived cultured mast cells to produce substantial levels of PGE2. This response is maximal at later time points 18-24 h after NGF activation. The ability of NGF to induce PGE2 is not dependent on mast cell degranulation. Other stimuli capable of inducing IL-6, such as LPS, do not induce production of this prostanoid. Inhibition of cyclooxygenase activity by PMC using either flurbiprofen or indomethacin inhibited both the NGF-induced PGE2 synthesis and the NGF-induced alterations in TNF-alpha and IL-6 production. These results suggest a role for mast cell-derived prostanoids in the regulation of local inflammatory responses and neuronal degeneration after tissue injury involving induction of NGF production.  (+info)

Cell degranulation is the process by which cells, particularly immune cells like mast cells and basophils, release granules containing inflammatory mediators in response to various stimuli. These mediators include histamine, leukotrienes, prostaglandins, and other chemicals that play a role in allergic reactions, inflammation, and immune responses. The activation of cell surface receptors triggers a signaling cascade that leads to the exocytosis of these granules, resulting in degranulation. This process is important for the immune system's response to foreign invaders and for the development of allergic reactions.

Mast cells are a type of white blood cell that are found in connective tissues throughout the body, including the skin, respiratory tract, and gastrointestinal tract. They play an important role in the immune system and help to defend the body against pathogens by releasing chemicals such as histamine, heparin, and leukotrienes, which help to attract other immune cells to the site of infection or injury. Mast cells also play a role in allergic reactions, as they release histamine and other chemicals in response to exposure to an allergen, leading to symptoms such as itching, swelling, and redness. They are derived from hematopoietic stem cells in the bone marrow and mature in the tissues where they reside.

4-Methoxy-N-methylphenethylamine (also known as 4-MeO-N-MEPEA or 4-MeO-PMA) is a synthetic psychoactive substance that belongs to the phenethylamine class. It is a designer drug, which means it is manufactured and distributed for recreational use as an alternative to illegal drugs.

It acts as a stimulant and entactogen, producing effects similar to those of MDMA (ecstasy) but with less potency. The compound has been linked to several cases of severe intoxication, including fatalities, due to its ability to increase heart rate and blood pressure, cause dehydration, hyperthermia, and serotonin syndrome.

It is important to note that the use of 4-Methoxy-N-methylphenethylamine and other designer drugs can be dangerous and illegal in many jurisdictions. Always consult a medical professional for accurate information regarding specific substances.

Histamine release is the process by which mast cells and basophils (types of white blood cells) release histamine, a type of chemical messenger or mediator, into the surrounding tissue fluid in response to an antigen-antibody reaction. This process is a key part of the body's immune response to foreign substances, such as allergens, and helps to initiate local inflammation, increase blood flow, and recruit other immune cells to the site of the reaction.

Histamine release can also occur in response to certain medications, physical trauma, or other stimuli. When histamine is released in large amounts, it can cause symptoms such as itching, sneezing, runny nose, watery eyes, and hives. In severe cases, it can lead to anaphylaxis, a life-threatening allergic reaction that requires immediate medical attention.

Anaphylaxis is a severe, life-threatening systemic allergic reaction that occurs suddenly after exposure to an allergen (a substance that triggers an allergic reaction) to which the person has previously been sensitized. The symptoms of anaphylaxis include rapid onset of symptoms such as itching, hives, swelling of the throat and tongue, difficulty breathing, wheezing, cough, chest tightness, rapid heartbeat, hypotension (low blood pressure), shock, and in severe cases, loss of consciousness and death. Anaphylaxis is a medical emergency that requires immediate treatment with epinephrine (adrenaline) and other supportive measures to stabilize the patient's condition.

Passive Cutaneous Anaphylaxis (PCA) is a type of localized or cutaneous hypersensitivity reaction that occurs when an individual who has been sensitized to a particular antigen is injected with the antigen along with a dye (usually Evans blue) and subsequently intravenously administered with a foreign protein, such as horse serum, that contains antibodies (IgG) against the antigen. The IgG antibodies passively transfer to the sensitized individual and bind to the antigen at the site of injection, forming immune complexes. These immune complexes then activate the complement system, leading to the release of mediators such as histamine, which causes localized vasodilation, increased vascular permeability, and extravasation of the dye into the surrounding tissues. As a result, a blue-colored wheal or skin blanching appears at the injection site, indicating a positive PCA reaction. This test is used to detect the presence of IgG antibodies in an individual's serum and to study the mechanisms of immune complex-mediated hypersensitivity reactions.

IgE receptors, also known as Fc epsilon RI receptors, are membrane-bound proteins found on the surface of mast cells and basophils. They play a crucial role in the immune response to parasitic infections and allergies. IgE receptors bind to the Fc region of immunoglobulin E (IgE) antibodies, which are produced by B cells in response to certain antigens. When an allergen cross-links two adjacent IgE molecules bound to the same IgE receptor, it triggers a signaling cascade that leads to the release of mediators such as histamine, leukotrienes, and prostaglandins. These mediators cause the symptoms associated with allergic reactions, including inflammation, itching, and vasodilation. IgE receptors are also involved in the activation of the adaptive immune response by promoting the presentation of antigens to T cells.

Immunoglobulin E (IgE) is a type of antibody that plays a key role in the immune response to parasitic infections and allergies. It is produced by B cells in response to stimulation by antigens, such as pollen, pet dander, or certain foods. Once produced, IgE binds to receptors on the surface of mast cells and basophils, which are immune cells found in tissues and blood respectively. When an individual with IgE antibodies encounters the allergen again, the cross-linking of IgE molecules bound to the FcεRI receptor triggers the release of mediators such as histamine, leukotrienes, prostaglandins, and various cytokines from these cells. These mediators cause the symptoms of an allergic reaction, such as itching, swelling, and redness. IgE also plays a role in protecting against certain parasitic infections by activating eosinophils, which can kill the parasites.

In summary, Immunoglobulin E (IgE) is a type of antibody that plays a crucial role in the immune response to allergens and parasitic infections, it binds to receptors on the surface of mast cells and basophils, when an individual with IgE antibodies encounters the allergen again, it triggers the release of mediators from these cells causing the symptoms of an allergic reaction.

Beta-N-Acetylhexosaminidases are a group of enzymes that play a role in the breakdown and recycling of complex carbohydrates in the body. Specifically, they help to break down gangliosides, which are a type of molecule found in cell membranes.

There are several different isoforms of beta-N-Acetylhexosaminidases, including A, B, and S. These isoforms are formed by different combinations of subunits, which can affect their activity and substrate specificity.

Mutations in the genes that encode for these enzymes can lead to a variety of genetic disorders, including Tay-Sachs disease and Sandhoff disease. These conditions are characterized by an accumulation of gangliosides in the brain, which can cause progressive neurological deterioration and death.

Treatment for these conditions typically involves managing symptoms and providing supportive care, as there is currently no cure. Enzyme replacement therapy has been explored as a potential treatment option, but its effectiveness varies depending on the specific disorder and the age of the patient.

Cromolyn sodium is a medication that belongs to a class of drugs known as mast cell stabilizers. It works by preventing the release of certain chemicals from mast cells, which are immune system cells found in various tissues throughout the body, including the skin, lungs, and gastrointestinal tract.

Mast cells play an important role in the body's allergic response. When a person is exposed to an allergen, such as pollen or pet dander, mast cells release chemicals like histamine, which can cause symptoms of an allergic reaction, such as itching, swelling, and inflammation.

Cromolyn sodium is used to prevent asthma attacks, hay fever, and other allergic reactions. It is often prescribed for people who have difficulty controlling their symptoms with other medications, such as inhaled corticosteroids or antihistamines.

The medication is available in various forms, including inhalers, nasal sprays, and eye drops. When used as an inhaler, cromolyn sodium is typically administered four times a day to prevent asthma symptoms. As a nasal spray or eye drop, it is usually used several times a day to prevent allergic rhinitis or conjunctivitis.

While cromolyn sodium can be effective in preventing allergic reactions, it does not provide immediate relief of symptoms. It may take several days or even weeks of regular use before the full benefits of the medication are felt.

Cytoplasmic granules are small, membrane-bound organelles or inclusions found within the cytoplasm of cells. They contain various substances such as proteins, lipids, carbohydrates, and genetic material. Cytoplasmic granules have diverse functions depending on their specific composition and cellular location. Some examples include:

1. Secretory granules: These are found in secretory cells and store hormones, neurotransmitters, or enzymes before they are released by exocytosis.
2. Lysosomes: These are membrane-bound organelles that contain hydrolytic enzymes for intracellular digestion of waste materials, foreign substances, and damaged organelles.
3. Melanosomes: Found in melanocytes, these granules produce and store the pigment melanin, which is responsible for skin, hair, and eye color.
4. Weibel-Palade bodies: These are found in endothelial cells and store von Willebrand factor and P-selectin, which play roles in hemostasis and inflammation.
5. Peroxisomes: These are single-membrane organelles that contain enzymes for various metabolic processes, such as β-oxidation of fatty acids and detoxification of harmful substances.
6. Lipid bodies (also called lipid droplets): These are cytoplasmic granules that store neutral lipids, such as triglycerides and cholesteryl esters. They play a role in energy metabolism and intracellular signaling.
7. Glycogen granules: These are cytoplasmic inclusions that store glycogen, a polysaccharide used for energy storage in animals.
8. Protein bodies: Found in plants, these granules store excess proteins and help regulate protein homeostasis within the cell.
9. Electron-dense granules: These are found in certain immune cells, such as mast cells and basophils, and release mediators like histamine during an allergic response.
10. Granules of unknown composition or function may also be present in various cell types.

Histamine is defined as a biogenic amine that is widely distributed throughout the body and is involved in various physiological functions. It is derived primarily from the amino acid histidine by the action of histidine decarboxylase. Histamine is stored in granules (along with heparin and proteases) within mast cells and basophils, and is released upon stimulation or degranulation of these cells.

Once released into the tissues and circulation, histamine exerts a wide range of pharmacological actions through its interaction with four types of G protein-coupled receptors (H1, H2, H3, and H4 receptors). Histamine's effects are diverse and include modulation of immune responses, contraction and relaxation of smooth muscle, increased vascular permeability, stimulation of gastric acid secretion, and regulation of neurotransmission.

Histamine is also a potent mediator of allergic reactions and inflammation, causing symptoms such as itching, sneezing, runny nose, and wheezing. Antihistamines are commonly used to block the actions of histamine at H1 receptors, providing relief from these symptoms.

Tryptase is a type of enzyme that is found in the cells called mast cells, which are a part of the immune system. Specifically, tryptase is a serine protease, which means it helps to break down other proteins in the body. Tryptase is often released during an allergic reaction or as part of an inflammatory response. It can be measured in the blood and is sometimes used as a marker for mast cell activation or degranulation. High levels of tryptase may indicate the presence of certain medical conditions, such as systemic mastocytosis or anaphylaxis.

Ketotifen is an antihistamine and mast cell stabilizer used in the prevention and treatment of allergic reactions. It works by blocking the release of histamine, a substance that causes allergic symptoms, and preventing the activation of mast cells, which play a key role in allergic responses. Ketotifen is available as an oral medication and is often used to treat chronic urticaria (hives) and other allergic conditions. It may also have some benefits in the treatment of asthma.

It's important to note that ketotifen should be taken under the supervision of a healthcare professional, as it can cause side effects such as drowsiness, dry mouth, and increased appetite. Additionally, it may interact with other medications, so it is important to inform your doctor of all medications you are taking before starting ketotifen.

Anti-allergic agents, also known as antihistamines, are a class of medications used to treat allergies. They work by blocking the action of histamine, a substance in the body that is released during an allergic reaction and causes symptoms such as itching, sneezing, runny nose, and watery eyes.

There are two main types of antihistamines: first-generation and second-generation. First-generation antihistamines, such as diphenhydramine (Benadryl) and chlorpheniramine (Chlor-Trimeton), can cause drowsiness and other side effects, such as dry mouth and blurred vision. They are typically used for the treatment of short-term symptoms, such as those caused by seasonal allergies or a mild reaction to an insect bite.

Second-generation antihistamines, such as loratadine (Claritin) and cetirizine (Zyrtec), are less likely to cause drowsiness and other side effects. They are often used for the long-term treatment of chronic allergies, such as those caused by dust mites or pet dander.

In addition to their use in treating allergies, antihistamines may also be used to treat symptoms of motion sickness, insomnia, and anxiety. It is important to follow the instructions on the label when taking antihistamines and to talk to a healthcare provider if you have any questions or concerns about using these medications.

Norbornanes are a class of compounds in organic chemistry that contain a norbornane skeleton, which is a bicyclic structure consisting of two fused cyclohexane rings. One of the rings is saturated, while the other contains a double bond. The name "norbornane" comes from the fact that it is a "nor" (short for "norcarene") derivative of bornane, which has a similar structure but with a methyl group attached to one of the carbon atoms in the saturated ring.

Norbornanes have a variety of applications in organic synthesis and medicinal chemistry. Some derivatives of norbornane have been explored for their potential as drugs, particularly in the areas of central nervous system agents and anti-inflammatory agents. However, there is no specific medical definition associated with "norbornanes" as they are a class of chemical compounds rather than a medical term or condition.

Basophils are a type of white blood cell that are part of the immune system. They are granulocytes, which means they contain granules filled with chemicals that can be released in response to an infection or inflammation. Basophils are relatively rare, making up less than 1% of all white blood cells.

When basophils become activated, they release histamine and other chemical mediators that can contribute to allergic reactions, such as itching, swelling, and redness. They also play a role in inflammation, helping to recruit other immune cells to the site of an infection or injury.

Basophils can be identified under a microscope based on their characteristic staining properties. They are typically smaller than other granulocytes, such as neutrophils and eosinophils, and have a multi-lobed nucleus with dark purple-staining granules in the cytoplasm.

While basophils play an important role in the immune response, abnormal levels of basophils can be associated with various medical conditions, such as allergies, infections, and certain types of leukemia.

The Basophil Degranulation Test is a medical test that measures the degree of degranulation (the release of granules and their contents) in basophils, a type of white blood cell, in response to a stimulus. This test is often used to diagnose allergies or hypersensitivity reactions, as basophils are known to degranulate when exposed to allergens or certain medications.

In this test, basophils are isolated from a patient's blood sample and then exposed to a suspected allergen or other stimuli. After incubation, the cells are stained with a dye that detects the presence of histamine or other mediators released during degranulation. The degree of staining is then measured and used as an indicator of basophil activation and degranulation.

It's important to note that this test is not commonly used in clinical practice due to its complexity, variability, and limited availability. Other tests, such as skin prick tests or blood tests for specific IgE antibodies, are more commonly used to diagnose allergies.

Complement C3a is a protein fragment that is generated during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by marking them for destruction and attracting immune cells to the site of infection or injury.

C3a is produced when the third component of the complement system (C3) is cleaved into two smaller fragments, C3a and C3b, during the complement activation cascade. C3a is a potent anaphylatoxin, which means it can cause the release of histamine and other mediators from mast cells and basophils, leading to inflammation, increased vascular permeability, and smooth muscle contraction.

C3a also has chemotactic properties, meaning it can attract immune cells such as neutrophils and monocytes to the site of complement activation. Additionally, C3a can modulate the activity of various immune cells, including dendritic cells, T cells, and B cells, and play a role in the regulation of the adaptive immune response.

It's important to note that while C3a has important functions in the immune response, uncontrolled or excessive activation of the complement system can lead to tissue damage and inflammation, contributing to the pathogenesis of various diseases such as autoimmune disorders, inflammatory diseases, and allergies.

Edema is the medical term for swelling caused by excess fluid accumulation in the body tissues. It can affect any part of the body, but it's most commonly noticed in the hands, feet, ankles, and legs. Edema can be a symptom of various underlying medical conditions, such as heart failure, kidney disease, liver disease, or venous insufficiency.

The swelling occurs when the capillaries leak fluid into the surrounding tissues, causing them to become swollen and puffy. The excess fluid can also collect in the cavities of the body, leading to conditions such as pleural effusion (fluid around the lungs) or ascites (fluid in the abdominal cavity).

The severity of edema can vary from mild to severe, and it may be accompanied by other symptoms such as skin discoloration, stiffness, and pain. Treatment for edema depends on the underlying cause and may include medications, lifestyle changes, or medical procedures.

Chymases are a type of enzyme that belong to the family of serine proteases. They are found in various tissues and organs, including the heart, lungs, and immune cells called mast cells. Chymases play a role in several physiological and pathological processes, such as inflammation, tissue remodeling, and blood pressure regulation.

One of the most well-known chymases is found in the mast cells and is often referred to as "mast cell chymase." This enzyme can cleave and activate various proteins, including angiotensin I to angiotensin II, a potent vasoconstrictor that increases blood pressure. Chymases have also been implicated in the development of cardiovascular diseases, such as hypertension and heart failure, as well as respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD).

In summary, chymases are a group of serine protease enzymes that play important roles in various physiological and pathological processes, particularly in inflammation, tissue remodeling, and blood pressure regulation.

Gliotoxin is not typically defined in the context of medical terminology, but it is a specific type of toxin that is produced by certain types of fungi. It's a mycotoxin, which is a toxic compound that is naturally produced by some types of molds (fungi).

Gliotoxin has been studied in the field of medical research due to its potential implications in various disease processes, particularly in relation to immune system function and inflammation. It has been found to have immunosuppressive effects and can inhibit the growth and activity of certain types of immune cells. This has led to interest in its potential role in conditions such as allergies, asthma, and various infectious diseases.

However, it's important to note that gliotoxin is not a term commonly used in medical diagnoses or treatments. Instead, it's a topic of research into possible mechanisms of disease and potential therapeutic targets.

Neutrophils are a type of white blood cell that are part of the immune system's response to infection. They are produced in the bone marrow and released into the bloodstream where they circulate and are able to move quickly to sites of infection or inflammation in the body. Neutrophils are capable of engulfing and destroying bacteria, viruses, and other foreign substances through a process called phagocytosis. They are also involved in the release of inflammatory mediators, which can contribute to tissue damage in some cases. Neutrophils are characterized by the presence of granules in their cytoplasm, which contain enzymes and other proteins that help them carry out their immune functions.

Histamine antagonists, also known as histamine blockers or H1-blockers, are a class of medications that work by blocking the action of histamine, a substance in the body that is released during an allergic reaction. Histamine causes many of the symptoms of an allergic response, such as itching, sneezing, runny nose, and hives. By blocking the effects of histamine, these medications can help to relieve or prevent allergy symptoms.

Histamine antagonists are often used to treat conditions such as hay fever, hives, and other allergic reactions. They may also be used to treat stomach ulcers caused by excessive production of stomach acid. Some examples of histamine antagonists include diphenhydramine (Benadryl), loratadine (Claritin), and famotidine (Pepcid).

It's important to note that while histamine antagonists can be effective at relieving allergy symptoms, they do not cure allergies or prevent the release of histamine. They simply block its effects. It's also worth noting that these medications can have side effects, such as drowsiness, dry mouth, and dizziness, so it's important to follow your healthcare provider's instructions carefully when taking them.

An allergen is a substance that can cause an allergic reaction in some people. These substances are typically harmless to most people, but for those with allergies, the immune system mistakenly identifies them as threats and overreacts, leading to the release of histamines and other chemicals that cause symptoms such as itching, sneezing, runny nose, rashes, hives, and difficulty breathing. Common allergens include pollen, dust mites, mold spores, pet dander, insect venom, and certain foods or medications. When a person comes into contact with an allergen, they may experience symptoms that range from mild to severe, depending on the individual's sensitivity to the substance and the amount of exposure.

Urticaria, also known as hives, is an allergic reaction that appears on the skin. It is characterized by the rapid appearance of swollen, pale red bumps or plaques (wheals) on the skin, which are often accompanied by itching, stinging, or burning sensations. These wheals can vary in size and shape, and they may change location and appear in different places over a period of hours or days. Urticaria is usually caused by an allergic reaction to food, medication, or other substances, but it can also be triggered by physical factors such as heat, cold, pressure, or exercise. The condition is generally harmless, but severe cases of urticaria may indicate a more serious underlying medical issue and should be evaluated by a healthcare professional.

Eosinophils are a type of white blood cell that play an important role in the body's immune response. They are produced in the bone marrow and released into the bloodstream, where they can travel to different tissues and organs throughout the body. Eosinophils are characterized by their granules, which contain various proteins and enzymes that are toxic to parasites and can contribute to inflammation.

Eosinophils are typically associated with allergic reactions, asthma, and other inflammatory conditions. They can also be involved in the body's response to certain infections, particularly those caused by parasites such as worms. In some cases, elevated levels of eosinophils in the blood or tissues (a condition called eosinophilia) can indicate an underlying medical condition, such as a parasitic infection, autoimmune disorder, or cancer.

Eosinophils are named for their staining properties - they readily take up eosin dye, which is why they appear pink or red under the microscope. They make up only about 1-6% of circulating white blood cells in healthy individuals, but their numbers can increase significantly in response to certain triggers.

Capillary permeability refers to the ability of substances to pass through the walls of capillaries, which are the smallest blood vessels in the body. These tiny vessels connect the arterioles and venules, allowing for the exchange of nutrients, waste products, and gases between the blood and the surrounding tissues.

The capillary wall is composed of a single layer of endothelial cells that are held together by tight junctions. The permeability of these walls varies depending on the size and charge of the molecules attempting to pass through. Small, uncharged molecules such as water, oxygen, and carbon dioxide can easily diffuse through the capillary wall, while larger or charged molecules such as proteins and large ions have more difficulty passing through.

Increased capillary permeability can occur in response to inflammation, infection, or injury, allowing larger molecules and immune cells to enter the surrounding tissues. This can lead to swelling (edema) and tissue damage if not controlled. Decreased capillary permeability, on the other hand, can lead to impaired nutrient exchange and tissue hypoxia.

Overall, the permeability of capillaries is a critical factor in maintaining the health and function of tissues throughout the body.

Hypersensitivity is an exaggerated or inappropriate immune response to a substance that is generally harmless to most people. It's also known as an allergic reaction. This abnormal response can be caused by various types of immunological mechanisms, including antibody-mediated reactions (types I, II, and III) and cell-mediated reactions (type IV). The severity of the hypersensitivity reaction can range from mild discomfort to life-threatening conditions. Common examples of hypersensitivity reactions include allergic rhinitis, asthma, atopic dermatitis, food allergies, and anaphylaxis.

Pyrilamine is an antihistamine drug that is primarily used to relieve allergic symptoms such as sneezing, itching, watery eyes, and runny nose. It works by blocking the action of histamine, a substance naturally produced by the body during an allergic reaction. Pyrilamine may also be used to treat motion sickness and to help with tension headaches or migraines.

Pyrilamine is available in various forms, including tablets, capsules, and syrup, and it can be taken with or without food. Common side effects of pyrilamine include dizziness, dry mouth, and drowsiness. It is important to avoid activities that require mental alertness, such as driving or operating heavy machinery, until you know how pyrilamine affects you.

Like all medications, pyrilamine should be taken under the supervision of a healthcare provider, who can determine the appropriate dosage and monitor for any potential side effects or interactions with other drugs. It is essential to follow the instructions provided by your healthcare provider carefully and not exceed the recommended dose.

Streptomycetaceae is a family of bacteria belonging to the order Actinomycetales. These bacteria are gram-positive, aerobic, and have a filamentous morphology that can resemble fungi. They are known for their ability to produce a wide variety of antibiotics and other secondary metabolites, making them important sources of drugs used in medicine and agriculture. Streptomycetaceae species are commonly found in soil and decaying vegetation, where they play important roles in nutrient cycling and decomposition.

Venules are very small blood vessels that carry oxygen-depleted blood from capillaries to veins. They have a diameter of 8-50 micrometers and are an integral part of the microcirculation system in the body. Venules merge together to form veins, which then transport the low-oxygen blood back to the heart.

Prostaglandin E (PGE) receptors are a subfamily of G protein-coupled receptors that are involved in various physiological and pathophysiological processes. The EP1 subtype of PGE receptors is one of four subtypes, along with EP2, EP3, and EP4.

EP1 receptors are widely expressed in various tissues, including the brain, heart, kidney, lung, and gastrointestinal tract. They are coupled to Gq proteins, which activate phospholipase C (PLC) and increase intracellular calcium levels upon activation.

EP1 receptor activation has been implicated in a variety of physiological responses, including vasoconstriction, increased heart rate and contractility, and inflammation. In the central nervous system, EP1 receptors have been shown to play a role in pain perception, thermoregulation, and neuroprotection.

Pharmacologically, selective EP1 receptor antagonists have been developed and are being investigated for their potential therapeutic benefits in various conditions, such as hypertension, myocardial ischemia, and inflammatory diseases.

In medical terms, the skin is the largest organ of the human body. It consists of two main layers: the epidermis (outer layer) and dermis (inner layer), as well as accessory structures like hair follicles, sweat glands, and oil glands. The skin plays a crucial role in protecting us from external factors such as bacteria, viruses, and environmental hazards, while also regulating body temperature and enabling the sense of touch.

Substance P is an undecapeptide neurotransmitter and neuromodulator, belonging to the tachykinin family of peptides. It is widely distributed in the central and peripheral nervous systems and is primarily found in sensory neurons. Substance P plays a crucial role in pain transmission, inflammation, and various autonomic functions. It exerts its effects by binding to neurokinin 1 (NK-1) receptors, which are expressed on the surface of target cells. Apart from nociception and inflammation, Substance P is also involved in regulating emotional behaviors, smooth muscle contraction, and fluid balance.

Allergic conjunctivitis is a type of conjunctivitis (inflammation of the conjunctiva, the membrane that covers the white part of the eye and the inner surface of the eyelids) caused by an allergic reaction to substances such as pollen, dust mites, or pet dander. It is often characterized by redness, itching, watering, and swelling of the eyes. In some cases, the eyes may also become sensitive to light. Allergic conjunctivitis is not contagious and can be treated with medications such as antihistamines, decongestants, or mast cell stabilizers.

Prostaglandin E (PGE) receptors are a type of G protein-coupled receptor that bind and respond to prostaglandin E, a lipid mediator involved in various physiological processes such as inflammation, pain perception, and smooth muscle contraction. The EP3 subtype is one of four subtypes of PGE receptors (EP1-EP4) and has been identified as playing a role in several important biological functions.

The EP3 receptor is widely expressed in various tissues, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. It can couple with multiple G proteins, leading to diverse downstream signaling pathways that regulate a range of cellular responses. The activation of EP3 receptors has been implicated in several physiological processes, such as:

1. Modulation of pain perception and inflammation: EP3 receptors can inhibit the release of pro-inflammatory cytokines and chemokines, which may contribute to their anti-inflammatory effects. However, they can also promote the production of other mediators that enhance pain signaling, making them a potential target for pain management therapies.
2. Regulation of smooth muscle contraction: EP3 receptors are involved in the regulation of smooth muscle tone in various organs, including the gastrointestinal tract and blood vessels. They can cause relaxation or contraction depending on the specific tissue and context.
3. Control of hormone secretion: EP3 receptors have been shown to regulate the release of several hormones, such as insulin, glucagon, and gonadotropins, which play crucial roles in metabolic homeostasis and reproduction.
4. Neuroprotection and neuroinflammation: In the central nervous system, EP3 receptors can have both neuroprotective and neurotoxic effects, depending on the context. They may contribute to the regulation of neuroinflammation and the development of certain neurological disorders.
5. Cardiovascular function: EP3 receptors are involved in the regulation of cardiovascular function, including blood pressure control and heart rate modulation.

Due to their diverse roles in various physiological processes, EP3 receptors have attracted significant interest as potential therapeutic targets for a wide range of diseases, such as inflammatory disorders, pain management, gastrointestinal dysfunction, metabolic disorders, and neurological conditions. However, further research is needed to fully understand their mechanisms of action and develop effective strategies for targeting them in clinical settings.

Ovalbumin is the major protein found in egg white, making up about 54-60% of its total protein content. It is a glycoprotein with a molecular weight of around 45 kDa and has both hydrophilic and hydrophobic regions. Ovalbumin is a single polypeptide chain consisting of 385 amino acids, including four disulfide bridges that contribute to its structure.

Ovalbumin is often used in research as a model antigen for studying immune responses and allergies. In its native form, ovalbumin is not allergenic; however, when it is denatured or degraded into smaller peptides through cooking or digestion, it can become an allergen for some individuals.

In addition to being a food allergen, ovalbumin has been used in various medical and research applications, such as vaccine development, immunological studies, and protein structure-function analysis.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Methysergide is a medication that belongs to a class of drugs called ergot alkaloids. It is primarily used for the prophylaxis (prevention) of migraine headaches. Methysergide works by narrowing blood vessels around the brain, which is thought to help prevent migraines.

The medical definition of Methysergide is:
A semisynthetic ergot alkaloid derivative used in the prophylaxis of migraine and cluster headaches. It has both agonist and antagonist properties at serotonin receptors, and its therapeutic effects are thought to be related to its ability to block the binding of serotonin to its receptors. However, methysergide can have serious side effects, including fibrotic reactions in various organs, such as the heart, lungs, and kidneys, so it is usually used only for short periods of time and under close medical supervision.

Exocytosis is the process by which cells release molecules, such as hormones or neurotransmitters, to the extracellular space. This process involves the transport of these molecules inside vesicles (membrane-bound sacs) to the cell membrane, where they fuse and release their contents to the outside of the cell. It is a crucial mechanism for intercellular communication and the regulation of various physiological processes in the body.

Phospholipase C gamma (PLCγ) is an enzyme that plays a crucial role in intracellular signaling transduction pathways, particularly in the context of growth factor receptor-mediated signals and immune cell activation. It is a member of the phospholipase C family, which hydrolyzes phospholipids into secondary messengers to mediate various cellular responses.

PLCγ has two isoforms, PLCγ1 and PLCγ2, encoded by separate genes. These isoforms share structural similarities but have distinct expression patterns and functions. PLCγ1 is widely expressed in various tissues, while PLCγ2 is primarily found in hematopoietic cells.

PLCγ is activated through tyrosine phosphorylation by receptor tyrosine kinases (RTKs) or non-receptor tyrosine kinases such as Src and Syk family kinases. Once activated, PLCγ hydrolyzes the membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), into two secondary messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates the release of calcium ions from intracellular stores, while DAG activates protein kinase C (PKC), leading to a cascade of downstream signaling events that regulate cell proliferation, differentiation, survival, and migration.

In summary, Phospholipase C gamma (PLCγ) is an enzyme involved in intracellular signaling pathways by generating secondary messengers IP3 and DAG upon activation through tyrosine phosphorylation, ultimately regulating various cellular responses.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Dermatitis is a general term that describes inflammation of the skin. It is often characterized by redness, swelling, itching, and tenderness. There are many different types of dermatitis, including atopic dermatitis (eczema), contact dermatitis, seborrheic dermatitis, and nummular dermatitis.

Atopic dermatitis is a chronic skin condition that often affects people with a family history of allergies, such as asthma or hay fever. It typically causes dry, scaly patches on the skin that can be extremely itchy.

Contact dermatitis occurs when the skin comes into contact with an irritant or allergen, such as poison ivy or certain chemicals. This type of dermatitis can cause redness, swelling, and blistering.

Seborrheic dermatitis is a common condition that causes a red, itchy rash, often on the scalp, face, or other areas of the body where oil glands are located. It is thought to be related to an overproduction of oil by the skin's sebaceous glands.

Nummular dermatitis is a type of eczema that causes round, coin-shaped patches of dry, scaly skin. It is more common in older adults and often occurs during the winter months.

Treatment for dermatitis depends on the underlying cause and severity of the condition. In some cases, over-the-counter creams or lotions may be sufficient to relieve symptoms. Prescription medications, such as corticosteroids or immunosuppressants, may be necessary in more severe cases. Avoiding triggers and irritants can also help prevent flare-ups of dermatitis.

An antigen is a substance (usually a protein) that is recognized as foreign by the immune system and stimulates an immune response, leading to the production of antibodies or activation of T-cells. Antigens can be derived from various sources, including bacteria, viruses, fungi, parasites, and tumor cells. They can also come from non-living substances such as pollen, dust mites, or chemicals.

Antigens contain epitopes, which are specific regions on the antigen molecule that are recognized by the immune system. The immune system's response to an antigen depends on several factors, including the type of antigen, its size, and its location in the body.

In general, antigens can be classified into two main categories:

1. T-dependent antigens: These require the help of T-cells to stimulate an immune response. They are typically larger, more complex molecules that contain multiple epitopes capable of binding to both MHC class II molecules on antigen-presenting cells and T-cell receptors on CD4+ T-cells.
2. T-independent antigens: These do not require the help of T-cells to stimulate an immune response. They are usually smaller, simpler molecules that contain repetitive epitopes capable of cross-linking B-cell receptors and activating them directly.

Understanding antigens and their properties is crucial for developing vaccines, diagnostic tests, and immunotherapies.

"Reagin" is an outdated term that was used to describe a type of antibody found in the blood serum of some individuals, particularly those who have had certain infectious diseases or who have allergies. These antibodies were known as "reaginic antibodies" and were characterized by their ability to cause a positive reaction in a test called the "Reagin test" or "Wassermann test."

The Reagin test was developed in the early 20th century and was used as a diagnostic tool for syphilis, a sexually transmitted infection caused by the bacterium Treponema pallidum. The test involved mixing a patient's serum with a suspension of cardiolipin, lecithin, and cholesterol - components derived from heart tissue. If reaginic antibodies were present in the patient's serum, they would bind to the cardiolipin component and form a complex that could be detected through a series of chemical reactions.

However, it was later discovered that reaginic antibodies were not specific to syphilis and could be found in individuals with other infectious diseases or allergies. As a result, the term "reagin" fell out of favor, and the test is no longer used as a diagnostic tool for syphilis. Instead, more specific and accurate tests, such as the Venereal Disease Research Laboratory (VDRL) test and the Treponema pallidum particle agglutination (TP-PA) assay, are now used to diagnose syphilis.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Mastocytosis is a group of rare disorders caused by the accumulation of abnormal number of mast cells in various tissues of the body, particularly the skin and internal organs such as the bone marrow, liver, spleen, and gastrointestinal tract. Mast cells are types of white blood cells that play an important role in the immune system, releasing chemicals like histamine, heparin, and leukotrienes during allergic reactions or injury to help protect the body. However, excessive accumulation of mast cells can lead to chronic inflammation, tissue damage, and various symptoms.

There are two main types of mastocytosis: cutaneous mastocytosis (CM) and systemic mastocytosis (SM). CM primarily affects the skin, causing redness, itching, hives, and other skin abnormalities. SM, on the other hand, involves internal organs and can be more severe, with symptoms such as diarrhea, stomach pain, fatigue, bone pain, and anaphylaxis (a life-threatening allergic reaction).

Mastocytosis is typically caused by genetic mutations that lead to the overproduction of mast cells. The diagnosis of mastocytosis usually involves a combination of physical examination, medical history, blood tests, skin biopsy, and bone marrow aspiration. Treatment options depend on the type and severity of the disease and may include antihistamines, corticosteroids, chemotherapy, targeted therapy, and in severe cases, stem cell transplantation.

Eosinophil peroxidase (EPO) is an enzyme that is primarily found in the granules of eosinophils, which are a type of white blood cell that plays a role in the immune response. EPO is involved in the destruction of certain types of parasites and also contributes to the inflammatory response in allergic reactions and other diseases.

EPO catalyzes the conversion of hydrogen peroxide to hypochlorous acid, which is a potent oxidizing agent that can kill or inhibit the growth of microorganisms. EPO also plays a role in the production of other reactive oxygen species, which can contribute to tissue damage and inflammation in certain conditions.

Elevated levels of EPO in tissues or bodily fluids may be indicative of eosinophil activation and degranulation, which can occur in various diseases such as asthma, allergies, parasitic infections, and some types of cancer. Measuring EPO levels can be useful in the diagnosis and monitoring of these conditions.

BALB/c is an inbred strain of laboratory mouse that is widely used in biomedical research. The strain was developed at the Institute of Cancer Research in London by Henry Baldwin and his colleagues in the 1920s, and it has since become one of the most commonly used inbred strains in the world.

BALB/c mice are characterized by their black coat color, which is determined by a recessive allele at the tyrosinase locus. They are also known for their docile and friendly temperament, making them easy to handle and work with in the laboratory.

One of the key features of BALB/c mice that makes them useful for research is their susceptibility to certain types of tumors and immune responses. For example, they are highly susceptible to developing mammary tumors, which can be induced by chemical carcinogens or viral infection. They also have a strong Th2-biased immune response, which makes them useful models for studying allergic diseases and asthma.

BALB/c mice are also commonly used in studies of genetics, neuroscience, behavior, and infectious diseases. Because they are an inbred strain, they have a uniform genetic background, which makes it easier to control for genetic factors in experiments. Additionally, because they have been bred in the laboratory for many generations, they are highly standardized and reproducible, making them ideal subjects for scientific research.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Neurotensin receptors are a type of G protein-coupled receptor (GPCR) that bind to the neuropeptide neurotensin. Neurotensin is a endogenous neuropeptide that is widely distributed in both the central and peripheral nervous systems, where it functions as a neurotransmitter or neuromodulator.

There are three subtypes of neurotensin receptors, NTS1, NTS2, and NTS3 (also known as sortilin), each with different binding affinities for neurotensin and distinct signaling properties.

NTS1 is a high-affinity receptor that is widely expressed in the brain and activates several intracellular signaling pathways, including the MAPK/ERK pathway, PI3K/Akt pathway, and the release of calcium ions from intracellular stores. NTS1 has been implicated in a variety of physiological functions, such as pain modulation, feeding behavior, and reward processing.

NTS2 is a low-affinity receptor that is predominantly expressed in the peripheral nervous system and activates different signaling pathways than NTS1, including the activation of phospholipase C and the release of intracellular calcium ions. NTS2 has been implicated in the regulation of gastrointestinal motility and secretion.

NTS3 is a sorting receptor that is involved in the intracellular trafficking of neurotensin and other ligands, but its role as a signaling receptor is less well understood.

Overall, neurotensin receptors play important roles in various physiological processes, and their dysregulation has been implicated in several pathological conditions, such as pain disorders, drug addiction, and gastrointestinal diseases.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

Hypersensitivity, Immediate: Also known as Type I hypersensitivity, it is an exaggerated and abnormal immune response that occurs within minutes to a few hours after exposure to a second dose of an allergen (a substance that triggers an allergic reaction). This type of hypersensitivity is mediated by immunoglobulin E (IgE) antibodies, which are produced by the immune system in response to the first exposure to the allergen. Upon subsequent exposures, these IgE antibodies bind to mast cells and basophils, leading to their degranulation and the release of mediators such as histamine, leukotrienes, and prostaglandins. These mediators cause a variety of symptoms, including itching, swelling, redness, and pain at the site of exposure, as well as systemic symptoms such as difficulty breathing, wheezing, and hypotension (low blood pressure). Examples of immediate hypersensitivity reactions include allergic asthma, hay fever, anaphylaxis, and some forms of food allergy.

Animal disease models are specialized animals, typically rodents such as mice or rats, that have been genetically engineered or exposed to certain conditions to develop symptoms and physiological changes similar to those seen in human diseases. These models are used in medical research to study the pathophysiology of diseases, identify potential therapeutic targets, test drug efficacy and safety, and understand disease mechanisms.

The genetic modifications can include knockout or knock-in mutations, transgenic expression of specific genes, or RNA interference techniques. The animals may also be exposed to environmental factors such as chemicals, radiation, or infectious agents to induce the disease state.

Examples of animal disease models include:

1. Mouse models of cancer: Genetically engineered mice that develop various types of tumors, allowing researchers to study cancer initiation, progression, and metastasis.
2. Alzheimer's disease models: Transgenic mice expressing mutant human genes associated with Alzheimer's disease, which exhibit amyloid plaque formation and cognitive decline.
3. Diabetes models: Obese and diabetic mouse strains like the NOD (non-obese diabetic) or db/db mice, used to study the development of type 1 and type 2 diabetes, respectively.
4. Cardiovascular disease models: Atherosclerosis-prone mice, such as ApoE-deficient or LDLR-deficient mice, that develop plaque buildup in their arteries when fed a high-fat diet.
5. Inflammatory bowel disease models: Mice with genetic mutations affecting intestinal barrier function and immune response, such as IL-10 knockout or SAMP1/YitFc mice, which develop colitis.

Animal disease models are essential tools in preclinical research, but it is important to recognize their limitations. Differences between species can affect the translatability of results from animal studies to human patients. Therefore, researchers must carefully consider the choice of model and interpret findings cautiously when applying them to human diseases.

IgG receptors, also known as Fcγ receptors (Fc gamma receptors), are specialized protein molecules found on the surface of various immune cells, such as neutrophils, monocytes, macrophages, and some lymphocytes. These receptors recognize and bind to the Fc region of IgG antibodies, one of the five classes of immunoglobulins in the human body.

IgG receptors play a crucial role in immune responses by mediating different effector functions, including:

1. Antibody-dependent cellular cytotoxicity (ADCC): IgG receptors on natural killer (NK) cells and other immune cells bind to IgG antibodies coated on the surface of virus-infected or cancer cells, leading to their destruction.
2. Phagocytosis: When IgG antibodies tag pathogens or foreign particles, phagocytes like neutrophils and macrophages recognize and bind to these immune complexes via IgG receptors, facilitating the engulfment and removal of the targeted particles.
3. Antigen presentation: IgG receptors on antigen-presenting cells (APCs) can internalize immune complexes, process the antigens, and present them to T cells, thereby initiating adaptive immune responses.
4. Inflammatory response regulation: IgG receptors can modulate inflammation by activating or inhibiting downstream signaling pathways in immune cells, depending on the specific type of Fcγ receptor and its activation state.

There are several types of IgG receptors (FcγRI, FcγRII, FcγRIII, and FcγRIV) with varying affinities for different subclasses of IgG antibodies (IgG1, IgG2, IgG3, and IgG4). The distinct functions and expression patterns of these receptors contribute to the complexity and fine-tuning of immune responses in the human body.

The peritoneal cavity is the potential space within the abdominal and pelvic regions, bounded by the parietal peritoneum lining the inner aspect of the abdominal and pelvic walls, and the visceral peritoneum covering the abdominal and pelvic organs. It contains a small amount of serous fluid that allows for the gliding of organs against each other during normal physiological activities such as digestion and movement. This cavity can become pathologically involved in various conditions, including inflammation, infection, hemorrhage, or neoplasia, leading to symptoms like abdominal pain, distention, or tenderness.

Lysosome-Associated Membrane Protein 1 (LAMP-1) is a type I transmembrane protein that is heavily glycosylated and primarily localized to the limiting membrane of lysosomes. It is one of the most abundant proteins in the lysosomal membrane, making up approximately 50% of its total protein mass. LAMP-1 plays a crucial role in maintaining the integrity and stability of the lysosomal membrane by preventing lysosomal enzyme leakage into the cytosol. It also participates in various cellular processes, including autophagy, cell death, and antigen presentation.

LAMP-1 is often used as a marker for late endosomes and lysosomes due to its specific localization in these organelles. The protein contains several structural features that are important for its function, such as a large luminal domain with multiple glycosylation sites, a transmembrane domain, and a short cytoplasmic tail. The cytoplasmic tail interacts with various proteins involved in intracellular trafficking, membrane fusion, and cytoskeletal organization, which contributes to the proper functioning of lysosomes and other related organelles.

"Rats, Inbred BN" are a strain of laboratory rats (Rattus norvegicus) that have been inbred for many generations to maintain a high level of genetic consistency and uniformity within the strain. The "BN" designation refers to the place where they were first developed, Bratislava, Czechoslovakia (now Slovakia).

These rats are often used in biomedical research because their genetic homogeneity makes them useful for studying the effects of specific genes or environmental factors on health and disease. They have been widely used as a model organism to study various physiological and pathophysiological processes, including hypertension, kidney function, immunology, and neuroscience.

Inbred BN rats are known for their low renin-angiotensin system activity, which makes them a useful model for studying hypertension and related disorders. They also have a unique sensitivity to dietary protein, making them a valuable tool for studying the relationship between diet and kidney function.

Overall, Inbred BN rats are an important tool in biomedical research, providing researchers with a consistent and well-characterized model organism for studying various aspects of human health and disease.

N-Formylmethionine Leucyl-Phenylalanine (fMLP) is not a medical condition, but rather a synthetic peptide that is often used in laboratory settings for research purposes. It is a formylated methionine residue linked to a leucine and phenylalanine tripeptide.

fMLP is a potent chemoattractant for certain types of white blood cells, including neutrophils and monocytes. When these cells encounter fMLP, they are stimulated to migrate towards the source of the peptide and release various inflammatory mediators. As such, fMLP is often used in studies of inflammation, immune cell function, and signal transduction pathways.

It's important to note that while fMLP has important research applications, it is not a substance that would be encountered or used in clinical medicine.

"Wistar rats" are a strain of albino rats that are widely used in laboratory research. They were developed at the Wistar Institute in Philadelphia, USA, and were first introduced in 1906. Wistar rats are outbred, which means that they are genetically diverse and do not have a fixed set of genetic characteristics like inbred strains.

Wistar rats are commonly used as animal models in biomedical research because of their size, ease of handling, and relatively low cost. They are used in a wide range of research areas, including toxicology, pharmacology, nutrition, cancer, cardiovascular disease, and behavioral studies. Wistar rats are also used in safety testing of drugs, medical devices, and other products.

Wistar rats are typically larger than many other rat strains, with males weighing between 500-700 grams and females weighing between 250-350 grams. They have a lifespan of approximately 2-3 years. Wistar rats are also known for their docile and friendly nature, making them easy to handle and work with in the laboratory setting.

Neutrophil infiltration is a pathological process characterized by the accumulation of neutrophils, a type of white blood cell, in tissue. It is a common feature of inflammation and occurs in response to infection, injury, or other stimuli that trigger an immune response. Neutrophils are attracted to the site of tissue damage by chemical signals called chemokines, which are released by damaged cells and activated immune cells. Once they reach the site of inflammation, neutrophils help to clear away damaged tissue and microorganisms through a process called phagocytosis. However, excessive or prolonged neutrophil infiltration can also contribute to tissue damage and may be associated with various disease states, including cancer, autoimmune disorders, and ischemia-reperfusion injury.

Proteinase-activated receptor 2 (PAR-2) is a type of G protein-coupled receptor that is widely expressed in various tissues, including the respiratory and gastrointestinal tracts, skin, and nervous system. PAR-2 can be activated by serine proteases such as trypsin, mast cell tryptase, and thrombin, which cleave the N-terminal extracellular domain of the receptor to expose a tethered ligand that binds to and activates the receptor.

Once activated, PAR-2 signaling can lead to a variety of cellular responses, including inflammation, pain, and altered ion channel activity. PAR-2 has been implicated in several physiological and pathophysiological processes, such as airway hyperresponsiveness, asthma, cough, gastrointestinal motility disorders, and skin disorders.

In summary, PAR-2 is a type of receptor that can be activated by serine proteases, leading to various cellular responses and involvement in several disease processes.

Splanchnic circulation refers to the blood flow to the visceral organs, including the gastrointestinal tract, pancreas, spleen, and liver. These organs receive a significant portion of the cardiac output, with approximately 25-30% of the total restingly going to the splanchnic circulation. The splanchnic circulation is regulated by a complex interplay of neural and hormonal mechanisms that help maintain adequate blood flow to these vital organs while also allowing for the distribution of blood to other parts of the body as needed.

The splanchnic circulation is unique in its ability to vasodilate and increase blood flow significantly in response to meals or other stimuli, such as stress or hormonal changes. This increased blood flow helps support the digestive process and absorption of nutrients. At the same time, the body must carefully regulate this blood flow to prevent a significant drop in blood pressure or overloading the heart with too much work.

Overall, the splanchnic circulation plays a critical role in maintaining the health and function of the body's vital organs, and dysregulation of this system can contribute to various diseases, including digestive disorders, liver disease, and cardiovascular disease.

Cytokines are a broad and diverse category of small signaling proteins that are secreted by various cells, including immune cells, in response to different stimuli. They play crucial roles in regulating the immune response, inflammation, hematopoiesis, and cellular communication.

Cytokines mediate their effects by binding to specific receptors on the surface of target cells, which triggers intracellular signaling pathways that ultimately result in changes in gene expression, cell behavior, and function. Some key functions of cytokines include:

1. Regulating the activation, differentiation, and proliferation of immune cells such as T cells, B cells, natural killer (NK) cells, and macrophages.
2. Coordinating the inflammatory response by recruiting immune cells to sites of infection or tissue damage and modulating their effector functions.
3. Regulating hematopoiesis, the process of blood cell formation in the bone marrow, by controlling the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells.
4. Modulating the development and function of the nervous system, including neuroinflammation, neuroprotection, and neuroregeneration.

Cytokines can be classified into several categories based on their structure, function, or cellular origin. Some common types of cytokines include interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, colony-stimulating factors (CSFs), and transforming growth factors (TGFs). Dysregulation of cytokine production and signaling has been implicated in various pathological conditions, such as autoimmune diseases, chronic inflammation, cancer, and neurodegenerative disorders.

Serine endopeptidases are a type of enzymes that cleave peptide bonds within proteins (endopeptidases) and utilize serine as the nucleophilic amino acid in their active site for catalysis. These enzymes play crucial roles in various biological processes, including digestion, blood coagulation, and programmed cell death (apoptosis). Examples of serine endopeptidases include trypsin, chymotrypsin, thrombin, and elastase.

Prostaglandin E (PGE) receptors are a type of G protein-coupled receptor that bind and respond to prostaglandin E, a lipid mediator involved in various physiological processes such as inflammation, pain perception, and fever. There are four subtypes of PGE receptors, designated EP1, EP2, EP3, and EP4.

The EP2 subtype of PGE receptor is a G protein-coupled receptor that specifically binds to prostaglandin E2 (PGE2) and activates the Gs protein, leading to an increase in intracellular cyclic AMP (cAMP) levels. The activation of EP2 receptors has been shown to have various effects on different tissues, including vasodilation, bronchodilation, and inhibition of platelet aggregation. In addition, EP2 receptors are involved in pain perception, inflammation, and neuroprotection.

EP2 receptors are widely expressed in the body, including in the brain, spinal cord, heart, lungs, gastrointestinal tract, and reproductive organs. They play a crucial role in various physiological processes, such as regulating blood flow, modulating immune responses, and controlling smooth muscle contraction. Dysregulation of EP2 receptor signaling has been implicated in several pathological conditions, including inflammatory diseases, pain disorders, and cancer.

Natural Killer (NK) cells are a type of lymphocyte, which are large granular innate immune cells that play a crucial role in the host's defense against viral infections and malignant transformations. They do not require prior sensitization to target and destroy abnormal cells, such as virus-infected cells or tumor cells. NK cells recognize their targets through an array of germline-encoded activating and inhibitory receptors that detect the alterations in the cell surface molecules of potential targets. Upon activation, NK cells release cytotoxic granules containing perforins and granzymes to induce target cell apoptosis, and they also produce a variety of cytokines and chemokines to modulate immune responses. Overall, natural killer cells serve as a critical component of the innate immune system, providing rapid and effective responses against infected or malignant cells.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

CD63 is a type of protein found on the surface of certain cells, including platelets and some immune cells. It is also known as granulophysin and is a member of the tetraspanin family of proteins. CD63 is often used as a marker for activated immune cells, particularly those involved in the immune response to viruses and other pathogens.

In the context of antigens, CD63 may be referred to as a target antigen, which is a molecule on the surface of a cell that can be recognized by the immune system. In this case, CD63 may be targeted by antibodies produced by the immune system in response to an infection or other stimulus.

It's important to note that while CD63 is often used as a marker for activated immune cells, it is not itself an antigen in the sense of being a foreign molecule that can elicit an immune response. Rather, it is a protein that can be targeted by the immune system in certain contexts.

Acute basophilic leukemia (ABL) is a rare and aggressive subtype of acute myeloid leukemia (AML), a type of cancer that affects the blood and bone marrow. In ABL, the malignancy originates from the transformation of hematopoietic stem cells into abnormal blast cells, specifically basophils, in the bone marrow. These blasts proliferate rapidly and disrupt normal blood cell production, leading to a significant decrease in functional red and white blood cells and platelets.

The medical definition of acute basophilic leukemia is:

A malignant neoplasm of hematopoietic stem cells characterized by the uncontrolled proliferation and accumulation of immature basophils (basophilic blasts) in the bone marrow, blood, and occasionally other tissues. This rapidly progressing disorder is accompanied by a decline in the production of normal blood cells, resulting in symptoms such as anemia, fatigue, infection, easy bruising, and bleeding. The diagnosis of ABL typically involves bone marrow aspiration and biopsy, cytogenetic analysis, immunophenotyping, and molecular genetic testing to confirm the presence of leukemic blasts and identify specific genetic abnormalities that can inform prognosis and treatment decisions.

Serine proteinase inhibitors, also known as serine protease inhibitors or serpins, are a group of proteins that inhibit serine proteases, which are enzymes that cut other proteins in a process called proteolysis. Serine proteinases are important in many biological processes such as blood coagulation, fibrinolysis, inflammation and cell death. The inhibition of these enzymes by serpin proteins is an essential regulatory mechanism to maintain the balance and prevent uncontrolled proteolytic activity that can lead to diseases.

Serpins work by forming a covalent complex with their target serine proteinases, irreversibly inactivating them. The active site of serpins contains a reactive center loop (RCL) that mimics the protease's target protein sequence and acts as a bait for the enzyme. When the protease cleaves the RCL, it gets trapped within the serpin structure, leading to its inactivation.

Serpin proteinase inhibitors play crucial roles in various physiological processes, including:

1. Blood coagulation and fibrinolysis regulation: Serpins such as antithrombin, heparin cofactor II, and protease nexin-2 control the activity of enzymes involved in blood clotting and dissolution to prevent excessive or insufficient clot formation.
2. Inflammation modulation: Serpins like α1-antitrypsin, α2-macroglobulin, and C1 inhibitor regulate the activity of proteases released during inflammation, protecting tissues from damage.
3. Cell death regulation: Some serpins, such as PI-9/SERPINB9, control apoptosis (programmed cell death) by inhibiting granzyme B, a protease involved in this process.
4. Embryonic development and tissue remodeling: Serpins like plasminogen activator inhibitor-1 (PAI-1) and PAI-2 regulate the activity of enzymes involved in extracellular matrix degradation during embryonic development and tissue remodeling.
5. Neuroprotection: Serpins such as neuroserpin protect neurons from damage by inhibiting proteases released during neuroinflammation or neurodegenerative diseases.

Dysregulation of serpins has been implicated in various pathological conditions, including thrombosis, emphysema, Alzheimer's disease, and cancer. Understanding the roles of serpins in these processes may provide insights into potential therapeutic strategies for treating these diseases.

"Cell count" is a medical term that refers to the process of determining the number of cells present in a given volume or sample of fluid or tissue. This can be done through various laboratory methods, such as counting individual cells under a microscope using a specialized grid called a hemocytometer, or using automated cell counters that use light scattering and electrical impedance techniques to count and classify different types of cells.

Cell counts are used in a variety of medical contexts, including hematology (the study of blood and blood-forming tissues), microbiology (the study of microscopic organisms), and pathology (the study of diseases and their causes). For example, a complete blood count (CBC) is a routine laboratory test that includes a white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin level, hematocrit value, and platelet count. Abnormal cell counts can indicate the presence of various medical conditions, such as infections, anemia, or leukemia.

Leukocytes, also known as white blood cells (WBCs), are a crucial component of the human immune system. They are responsible for protecting the body against infections and foreign substances. Leukocytes are produced in the bone marrow and circulate throughout the body in the bloodstream and lymphatic system.

There are several types of leukocytes, including:

1. Neutrophils - These are the most abundant type of leukocyte and are primarily responsible for fighting bacterial infections. They contain enzymes that can destroy bacteria.
2. Lymphocytes - These are responsible for producing antibodies and destroying virus-infected cells, as well as cancer cells. There are two main types of lymphocytes: B-lymphocytes and T-lymphocytes.
3. Monocytes - These are the largest type of leukocyte and help to break down and remove dead or damaged tissues, as well as microorganisms.
4. Eosinophils - These play a role in fighting parasitic infections and are also involved in allergic reactions and inflammation.
5. Basophils - These release histamine and other chemicals that cause inflammation in response to allergens or irritants.

An abnormal increase or decrease in the number of leukocytes can indicate an underlying medical condition, such as an infection, inflammation, or a blood disorder.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

A "mutant strain of mice" in a medical context refers to genetically engineered mice that have specific genetic mutations introduced into their DNA. These mutations can be designed to mimic certain human diseases or conditions, allowing researchers to study the underlying biological mechanisms and test potential therapies in a controlled laboratory setting.

Mutant strains of mice are created through various techniques, including embryonic stem cell manipulation, gene editing technologies such as CRISPR-Cas9, and radiation-induced mutagenesis. These methods allow scientists to introduce specific genetic changes into the mouse genome, resulting in mice that exhibit altered physiological or behavioral traits.

These strains of mice are widely used in biomedical research because their short lifespan, small size, and high reproductive rate make them an ideal model organism for studying human diseases. Additionally, the mouse genome has been well-characterized, and many genetic tools and resources are available to researchers working with these animals.

Examples of mutant strains of mice include those that carry mutations in genes associated with cancer, neurodegenerative disorders, metabolic diseases, and immunological conditions. These mice provide valuable insights into the pathophysiology of human diseases and help advance our understanding of potential therapeutic interventions.

Bronchial hyperresponsiveness (BHR) or bronchial hyperreactivity (BH) is a medical term that refers to the increased sensitivity and exaggerated response of the airways to various stimuli. In people with BHR, the airways narrow (constrict) more than usual in response to certain triggers such as allergens, cold air, exercise, or irritants like smoke or fumes. This narrowing can cause symptoms such as wheezing, coughing, chest tightness, and shortness of breath.

BHR is often associated with asthma and other respiratory conditions, including chronic obstructive pulmonary disease (COPD) and bronchiectasis. It is typically diagnosed through a series of tests that measure the degree of airway narrowing in response to various stimuli. These tests may include spirometry, methacholine challenge test, or histamine challenge test.

BHR can be managed with medications such as bronchodilators and anti-inflammatory drugs, which help to relax the muscles around the airways and reduce inflammation. It is also important to avoid triggers that can exacerbate symptoms and make BHR worse.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

I must clarify that the term "Guinea Pigs" is not typically used in medical definitions. However, in colloquial or informal language, it may refer to people who are used as the first to try out a new medical treatment or drug. This is known as being a "test subject" or "in a clinical trial."

In the field of scientific research, particularly in studies involving animals, guinea pigs are small rodents that are often used as experimental subjects due to their size, cost-effectiveness, and ease of handling. They are not actually pigs from Guinea, despite their name's origins being unclear. However, they do not exactly fit the description of being used in human medical experiments.

Neutrophil activation refers to the process by which neutrophils, a type of white blood cell, become activated in response to a signal or stimulus, such as an infection or inflammation. This activation triggers a series of responses within the neutrophil that enable it to carry out its immune functions, including:

1. Degranulation: The release of granules containing enzymes and other proteins that can destroy microbes.
2. Phagocytosis: The engulfment and destruction of microbes through the use of reactive oxygen species (ROS) and other toxic substances.
3. Formation of neutrophil extracellular traps (NETs): A process in which neutrophils release DNA and proteins to trap and kill microbes outside the cell.
4. Release of cytokines and chemokines: Signaling molecules that recruit other immune cells to the site of infection or inflammation.

Neutrophil activation is a critical component of the innate immune response, but excessive or uncontrolled activation can contribute to tissue damage and chronic inflammation.

Inflammation mediators are substances that are released by the body in response to injury or infection, which contribute to the inflammatory response. These mediators include various chemical factors such as cytokines, chemokines, prostaglandins, leukotrienes, and histamine, among others. They play a crucial role in regulating the inflammatory process by attracting immune cells to the site of injury or infection, increasing blood flow to the area, and promoting the repair and healing of damaged tissues. However, an overactive or chronic inflammatory response can also contribute to the development of various diseases and conditions, such as autoimmune disorders, cardiovascular disease, and cancer.

Lactoferrin is a glycoprotein that belongs to the transferrin family. It is an iron-binding protein found in various exocrine secretions such as milk, tears, and saliva, as well as in neutrophils, which are a type of white blood cell involved in immune response. Lactoferrin plays a role in iron homeostasis, antimicrobial activity, and anti-inflammatory responses. It has the ability to bind free iron, which can help prevent bacterial growth by depriving them of an essential nutrient. Additionally, lactoferrin has been shown to have direct antimicrobial effects against various bacteria, viruses, and fungi. Its role in the immune system also includes modulating the activity of immune cells and regulating inflammation.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

A lung is a pair of spongy, elastic organs in the chest that work together to enable breathing. They are responsible for taking in oxygen and expelling carbon dioxide through the process of respiration. The left lung has two lobes, while the right lung has three lobes. The lungs are protected by the ribcage and are covered by a double-layered membrane called the pleura. The trachea divides into two bronchi, which further divide into smaller bronchioles, leading to millions of tiny air sacs called alveoli, where the exchange of gases occurs.

Calcium signaling is the process by which cells regulate various functions through changes in intracellular calcium ion concentrations. Calcium ions (Ca^2+^) are crucial second messengers that play a critical role in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and programmed cell death (apoptosis).

Intracellular calcium levels are tightly regulated by a complex network of channels, pumps, and exchangers located on the plasma membrane and intracellular organelles such as the endoplasmic reticulum (ER) and mitochondria. These proteins control the influx, efflux, and storage of calcium ions within the cell.

Calcium signaling is initiated when an external signal, such as a hormone or neurotransmitter, binds to a specific receptor on the plasma membrane. This interaction triggers the opening of ion channels, allowing extracellular Ca^2+^ to flow into the cytoplasm. In some cases, this influx of calcium ions is sufficient to activate downstream targets directly. However, in most instances, the increase in intracellular Ca^2+^ serves as a trigger for the release of additional calcium from internal stores, such as the ER.

The release of calcium from the ER is mediated by ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), which are activated by specific second messengers generated in response to the initial external signal. The activation of these channels leads to a rapid increase in cytoplasmic Ca^2+^, creating a transient intracellular calcium signal known as a "calcium spark" or "calcium puff."

These localized increases in calcium concentration can then propagate throughout the cell as waves of elevated calcium, allowing for the spatial and temporal coordination of various cellular responses. The duration and amplitude of these calcium signals are finely tuned by the interplay between calcium-binding proteins, pumps, and exchangers, ensuring that appropriate responses are elicited in a controlled manner.

Dysregulation of intracellular calcium signaling has been implicated in numerous pathological conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer. Therefore, understanding the molecular mechanisms governing calcium homeostasis and signaling is crucial for the development of novel therapeutic strategies targeting these diseases.

Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is characterized by the following signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function). The process involves the activation of the immune system, recruitment of white blood cells, and release of inflammatory mediators, which contribute to the elimination of the injurious stimuli and initiation of the healing process. However, uncontrolled or chronic inflammation can also lead to tissue damage and diseases.

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter that is found primarily in the gastrointestinal (GI) tract, blood platelets, and the central nervous system (CNS) of humans and other animals. It is produced by the conversion of the amino acid tryptophan to 5-hydroxytryptophan (5-HTP), and then to serotonin.

In the CNS, serotonin plays a role in regulating mood, appetite, sleep, memory, learning, and behavior, among other functions. It also acts as a vasoconstrictor, helping to regulate blood flow and blood pressure. In the GI tract, it is involved in peristalsis, the contraction and relaxation of muscles that moves food through the digestive system.

Serotonin is synthesized and stored in serotonergic neurons, which are nerve cells that use serotonin as their primary neurotransmitter. These neurons are found throughout the brain and spinal cord, and they communicate with other neurons by releasing serotonin into the synapse, the small gap between two neurons.

Abnormal levels of serotonin have been linked to a variety of disorders, including depression, anxiety, schizophrenia, and migraines. Medications that affect serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs), are commonly used to treat these conditions.

Cell adhesion refers to the binding of cells to extracellular matrices or to other cells, a process that is fundamental to the development, function, and maintenance of multicellular organisms. Cell adhesion is mediated by various cell surface receptors, such as integrins, cadherins, and immunoglobulin-like cell adhesion molecules (Ig-CAMs), which interact with specific ligands in the extracellular environment. These interactions lead to the formation of specialized junctions, such as tight junctions, adherens junctions, and desmosomes, that help to maintain tissue architecture and regulate various cellular processes, including proliferation, differentiation, migration, and survival. Disruptions in cell adhesion can contribute to a variety of diseases, including cancer, inflammation, and degenerative disorders.

Phosphoric monoester hydrolases are a class of enzymes that catalyze the hydrolysis of phosphoric monoesters into alcohol and phosphate. This class of enzymes includes several specific enzymes, such as phosphatases and nucleotidases, which play important roles in various biological processes, including metabolism, signal transduction, and regulation of cellular processes.

Phosphoric monoester hydrolases are classified under the EC number 3.1.3 by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB). The enzymes in this class share a common mechanism of action, which involves the nucleophilic attack on the phosphorus atom of the substrate by a serine or cysteine residue in the active site of the enzyme. This results in the formation of a covalent intermediate, which is then hydrolyzed to release the products.

Phosphoric monoester hydrolases are important therapeutic targets for the development of drugs that can modulate their activity. For example, inhibitors of phosphoric monoester hydrolases have been developed as potential treatments for various diseases, including cancer, neurodegenerative disorders, and infectious diseases.

A plant extract is a preparation containing chemical constituents that have been extracted from a plant using a solvent. The resulting extract may contain a single compound or a mixture of several compounds, depending on the extraction process and the specific plant material used. These extracts are often used in various industries including pharmaceuticals, nutraceuticals, cosmetics, and food and beverage, due to their potential therapeutic or beneficial properties. The composition of plant extracts can vary widely, and it is important to ensure their quality, safety, and efficacy before use in any application.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

... cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms. Degranulation in mast cells is part of ... Cell+Degranulation at the U.S. National Library of Medicine Medical Subject Headings (MeSH) (All articles with dead external ... Cytotoxic T cells and NK cells release molecules like perforin and granzymes by a process of directed exocytosis to kill ... via the activation of tyrosine kinases within the cell. The mast cell releases a mixture of compounds, including histamine, ...
It enhances B cell immunoglobulin production and proliferation. OPN also induces mast cell degranulation. IgE-mediated ... February 2008). "Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells". ... These integrin receptors are present on a number of immune cells such as mast cells, neutrophils, and T cells. It is also ... OPN blocks the activation-induced cell death of macrophages and T cells as well as fibroblasts and endothelial cells exposed to ...
... degranulation of mast cells, basophils, and eosinophils; and other processes). In a new development in the field of antibody- ... The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors ... The Fc region is, therefore, sometimes incorrectly termed the "fragment constant region". Fc binds to various cell receptors ... In this way, it mediates different physiological effects of antibodies (detection of opsonized particles; cell lysis; ...
... as occurs in necrotic cell death. Extracellular ATP triggers mast cell degranulation by signaling through P2X7 receptors. ... are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to ... and it can lead to increased expression of cell adhesion molecules (ICAM-1, VCAM-1) on endothelial cells. DNA and RNA: The ... doi:10.1016/j.cell.2014.03.011. PMC 4056765. PMID 24679531. Bernard JJ, Cowing-Zitron C, Nakatsuji T, Muehleisen B, Muto J, ...
It inhibits the degranulation of mast cells. It has a quinidine-like anti-arrhythmic effect. It has vasodilatory properties and ... Tetrandrine has also been shown to inhibit entry of Ebola virus into host cells in vitro and showed therapeutic efficacy ... "The study of anti-tumor effect of Tetrandrine combined with Nedaplatin on human liver cancer cell line 7402". Zhong Yao Cai = ... "Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment". Science. 347 (6225): 995-998 ...
Wareham KJ, Seward EP (June 2016). "P2X7 receptors induce degranulation in human mast cells". Purinergic Signalling. 12 (2): ... On T cells activation of P2X7 receptors can activate the T cells or cause T cell differentiation, can affect T cell migration ... Boison D, Chen JF, Fredholm BB (July 2010). "Adenosine signaling and function in glial cells". Cell Death and Differentiation. ... mast cell degranulation, and inflammation. The P2X7 subunits can form homomeric receptors only with a typical P2X receptor ...
A unique, stimulus-specific set of mast cell mediators is released through degranulation following the activation of cell ... Other neoplastic disorders associated with mast cells include mast cell sarcoma and mast cell leukemia. Mast cell activation ... connective tissue-type mast cells and mucosal mast cells. The activities of the latter are dependent on T-cells. Mast cells are ... "Distinguishing mast cell and granulocyte differentiation at the single-cell level". Cell Stem Cell. 6 (4): 361-8. doi:10.1016/j ...
Klein, Ofir; Sagi-Eisenberg, Ronit (2019-03-18). "Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis". ... mainly T helper 2 cells (Th2 cells), B cells and mast cells. In a nut shell, as a stimulus, such as an allergen comes into ... where T cells interact with dendritic cells, the dendritic cells will present a specific antigen from the allergen to Th2 cells ... another type of immune cell to differentiate intoallergen-specific memory B cells and plasma cells. The plasma cells will then ...
August 2004). "Degranulation of paneth cells via toll-like receptor 9". The American Journal of Pathology. 165 (2): 373-381. ... Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some ... it has been shown that Paneth cells clear dying cells via apoptotic cell uptake. The pahgocytic function of Paneth cells was ... Like the other epithelial cell lineages in the small intestine, Paneth cells originate at the stem cell region near the bottom ...
The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell , and shows anti- ... For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing histamine; at ... The MCD peptide has an immunotoxic effect on mast cells by releasing histamine from these cells. MCD peptide has also been ... Buku, A; Priceb, JA; Mendlowitzc, M; Masurd, S (2001). "Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors ...
It is in eukaryotic cells. It pumps protons. It is usually in internal plasma membranes. The V1 portion of the protein "is an ... Neutrophils, "degranulation," and "phagocytosis" from protein kinase C increases vATPase. vATPase activity creates immune ... Molecular Cell Biology. 3 (2): 94-103. doi:10.1038/nrm729. PMID 11836511. S2CID 21122465. Kawasaki-Nishi S, Nishi T, Forgac M ( ... The enzyme serves three main functions within the cell. First, ATP is hydrolyzed by this enzyme. This means that ATP is broken ...
The reaction of IgE with Aspergillus antigens results in mast cell degranulation with bronchoconstriction and increased ... These cytokines up-regulate mast cell degranulation, exacerbating respiratory decline. Aspergillus also uses a number of ... "Lack of IL-4 receptor expression on T helper cells reduces T helper 2 cell polyfunctionality and confers resistance in allergic ... Type 2 T helper cells appear to play an important role in ABPA due to an increased sensitivity to interleukin (IL) 4 and IL-5. ...
Puri N, Kruhlak MJ, Whiteheart SW, Roche PA (Nov 2003). "Mast cell degranulation requires N-ethylmaleimide-sensitive factor- ... The Journal of Cell Biology. 157 (1): 45-62. doi:10.1083/jcb.200112127. PMC 2173270. PMID 11927603. Xu Y, Martin S, James DE, ... The Journal of Cell Biology. 157 (1): 45-62. doi:10.1083/jcb.200112127. PMC 2173270. PMID 11927603. Xu Y, Martin S, James DE, ... Molecular Biology of the Cell. 15 (9): 4011-22. doi:10.1091/mbc.E03-12-0876. PMC 515336. PMID 15215310. Kimura K, Wakamatsu A, ...
In mast cells, FYB regulates cell adhesion as well as degranulation. In T cells, FYB allows for cell adhesion and migration ... The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells. FYB is a multifunctional ... FYB regulates cytokine production in T cells as well as in activated NK cells through the FYN-ADAP axis. In T cells, after TCR ... or the transfer of signals from outside the cell to inside the cell by integrin. FYB can also bind to SKAP1, which allows SKAP1 ...
CD23 and CD25 are targets of Der p 1, which cleaves these receptors from the surfaces of active B cells and T cells, ... Der f 1 also triggers an immune response through eosinophil degranulation. Eur m 1 is secreted by the Mayne's house dust mite ... Eur m 1 provokes allergic responses from T cells. Der p 1 and Der f 1 show only low levels of cross-reactivity with Eur m 1. ... It has been suggested that the mite's gastrointestinal cells produce Der p 1. In the mite, Der p 1 is responsible for the ...
The reaction as a whole is driven by mast cell degranulation. Subsequent investigation demonstrated that complement, ... Complement-dependent and -independent mast cell involvement". Journal of Immunology. 152 (3): 1380-1384. doi:10.4049/jimmunol. ... reaction indirectly because the resultant signaling alters the ratio of activating to inhibitory Fc receptors on effector cells ...
The activated neutrophils can then adhere to endothelial cells where degranulation occurs. This releases free oxygen radicals ... Based on the above observations and that ANCA reactive B-cells can be found in circulation in patients with AAV, an alternative ... Hurtado, Plinio; Nitschke, J.; Hurtado-Perez, E.; Peh, C.A. (April 2013). "ANCA reactive B cells and neutrophils cross-talk in ... The same study found that clinical relapse in some patients were in association with the return of circulating B-cells. ...
"Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation". British Journal of Pharmacology. 147 ( ... May 2012). "Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis". Cell Stem Cell ... bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow ... Most mesenchymal cell or "MSC" preps only contain a minority fraction of true multipotent stem cells, with most cells being ...
CERK has also been found to participate in the calcium-dependent degranulation of mast cells. Sugiura M, Kono K, Liu H, ... However, CERK expression varies per cell line. In contrast to SH-SY5Y neuroblastoma cells, HL60 leukemia cells demonstrated no ... CERK activity has primarily been observed within human neutrophils, cerebrum granule cells, and epithelium-derived lung cells. ... "Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells". J. Biol. Chem. 279 (17): 17570-7. doi:10.1074/ ...
Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. ... "Ethanol-induced inhibition of cytokine release and protein degranulation in human neutrophils". Journal of Leukocyte Biology. ... At the cell surface, pro-TNF-α is biologically active, and is able to induce immune responses via juxtacrine intercellular ... ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and ...
Degranulation of mast cells contributing to lung damage has also been observed. The term "third-hand smoke" was recently coined ... Eren, U.; Kum, S.; Sandikci, M.; Kara, E. (2006). "Effects of long-term passive smoking on the mast cells in rat lungs". Revue ... "p53 expression and environmental tobacco smoke exposure in feline oral squamous cell carcinoma". Vet Pathol. 41 (3): 209-14. ...
Neurotensin is involved in many processes including mast cell degranulation and regulation of central nervous system ... "Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress". Urology. 53 (5): 1035-40. ... "A neurotensin receptor antagonist inhibits acute immobilization stress-induced cardiac mast cell degranulation, a corticotropin ... It is a 78-kDa enzyme, widely distributed in mammalian tissues and found in various subcellular locations that vary with cell ...
... depending on the cell type, various other responses such as degranulation (i.e. release of granule-bound enzymes), oxidative ... Like other cell signaling agents, 5-oxo-ETE is made by a cell and then feeds back to stimulate its parent cell (see Autocrine ... HETE producing cells and human PC-3 prostate cancer cells, platelets, and monocyte-derived dendritic cells as the oxidizing ... airway epithelial cells and smooth muscle cells, vascular endothelial cells, and skin keratinocytes have been found and/or ...
... causes mast cell and eosinophil degranulation, leading to pro-inflammatory cytokine release. Infection may ...
Activation of MRGPRX2 leads to mast cell degranulation with subsequent pseudo-allergic reactions. MAS1 oncogene GRCh38: Ensembl ... It is most abundant on cutaneous mast cells. Agonists are gyrase inhibitors like ciprofloxacin and non-depolarizing ... Cell. 106 (5): 619-632. doi:10.1016/S0092-8674(01)00483-4. PMID 11551509. "Entrez Gene: MRGPRX2 MAS-related GPR, member X2". ...
The inner cell surface of the granules becomes the outer cell surface of the basophil /mast cell during degranulation process. ... The cells are activated and start degranulation when the IgE antibody, bound to an allergen which can bind to the specific ... There are receptors (FcεR) for the constant region of IgE, the Fc region, on several types of cells, including Mast cells and ... This is why basophils are considered with mast cells to be the key cells in allergic diseases. Immunoglobulin E (IgE) is a ...
"Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation". Molecular and Cellular Biology. 22 ... SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This ... for example T cell receptor (TCR) and CD79a/b. SHIP1 does not bind only to intracellular chains of cell surface receptor. Its ... van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M (November 2000). "Stem cell factor induces ...
Decreasing pH is associated with an increase in mast cell degranulation, a key component to the immune response, and one study ... Welle M (March 1997). "Development, significance, and heterogeneity of mast cells with particular regard to the mast cell- ... a serious form of physical allergy associated with mast cell degranulation". The Journal of Allergy and Clinical Immunology. 75 ... Mast cells are structurally different in the gut than those found in the skin or skeletal muscles, and thus could be induced by ...
"Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation". Mol. Cell. Biol. 22 (12): 3970-80. ... "Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration". J. Cell ... Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein ... Studies both in human and mice demonstrate that this kinase is involved in B cell signaling and in the regulation of growth, ...
... nutrition and other cell-cell communications. It has been found that many pathogens have converged on similar virulence factors ... They bind to receptors on monocytes causing the release of inflammatory mediators which induce degranulation. As part of this ... and hemolysins which break down a variety of host cells, including red blood cells. A major group of virulence factors are ... this includes leukocidin-mediated cell death) entry into and exit out of cells (if the pathogen is an intracellular one) obtain ...

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