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Journal of the European Academy of... Nov 1999To review our present knowledge about mastocyte origin, mastocytosis classification and management. (Review)
Review
AIM
To review our present knowledge about mastocyte origin, mastocytosis classification and management.
METHODS
Literature review.
RESULTS
Mastocytoses are chronic and recurrent disorders with symptoms which might either be limited only to the skin or to internal organs as well. The mastocytes, coming from bone marrow progenitor cells, migrate to tissues where they participate in inflammation and in cellular immunity as well as in the metabolism of connective and osseous tissues. Their proliferation causes the appearance of mastocytoses. The classification of the clinical manifestations of the mastocytoses into cutaneous, reactive (under the influence of the degranulator factors) and systemic disease, facilitates dialog among clinicians. Determination of prognosis and appropriate therapeutic regimens depend on individual features.
CONCLUSIONS
Mastocytosis diagnosis is verified by histological study of skin lesion biopsy material. Management is symptomatic and unfortunately does not eradicate the disease.
Topics: Bone and Bones; Cell Degranulation; Cell Division; Cell Movement; Chronic Disease; Connective Tissue; Humans; Immunity, Cellular; Mast Cells; Mastocytosis; Prognosis; Recurrence
PubMed: 10642051
DOI: 10.1111/j.1468-3083.1999.tb00878.x -
PloS One 2016Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key...
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation. However, it is completely unknown how SR-B1 mediates mast cell degranulation and the intracellular signaling pathways involved. In the current study, we hypothesized that SR-B1 interaction with AgNPs directs mast cell degranulation through activation of signal transduction pathways that culminate in an increase in intracellular calcium signal leading to mast cell degranulation. For these studies, we utilized bone marrow-derived mast cells (BMMC) isolated from C57Bl/6 mice and RBL-2H3 cells (rat basophilic leukemia cell line). Our data support our hypothesis and show that AgNP-directed mast cell degranulation involves activation of PI3K, PLCγ and an increase in intracellular calcium levels. Moreover, we found that influx of extracellular calcium is required for the cells to degranulate in response to AgNP exposure and is mediated at least partially via the CRAC channels. Taken together, our results provide new insights into AgNP-induced mast cell activation that are key for designing novel ENMs that are devoid of immune system activation.
Topics: Animals; Calcium; Calcium Signaling; Cell Degranulation; Cell Line; Humans; Immunity, Innate; Mast Cells; Metal Nanoparticles; Mice; Phosphatidylinositol 3-Kinases; Rats; Receptors, IgE; Scavenger Receptors, Class B; Silver
PubMed: 27907088
DOI: 10.1371/journal.pone.0167366 -
Journal of Immunology (Baltimore, Md. :... Nov 2005Mast cell degranulation can initiate an acute inflammatory response and contribute to the progression of chronic diseases. Alteration in the cellular programs that...
Mast cell degranulation can initiate an acute inflammatory response and contribute to the progression of chronic diseases. Alteration in the cellular programs that determine the requirement for mast cell degranulation would therefore have the potential to dramatically impact disease severity. Mast cells are exposed to increased levels of PGE2 during inflammation. We show that although PGE2 does not trigger the degranulation of dermal mast cells of young animals, in older mice, PGE2 is a potent mast cell stimulator. Intradermal administration of PGE2 leads to an EP3 receptor-dependent degranulation of mast cells, with the number of degranulated cells approaching levels observed in IgE- and Ag-treated controls. Taken together, these studies suggest that the ability of PGE2 to initiate mast cell degranulation changes in the aging animal. Therefore, elevated PGE2 levels might provide an important pathway by which mast cells are engaged to participate in inflammatory responses in the elderly patient.
Topics: Age Factors; Alprostadil; Animals; Cell Degranulation; Dermatitis; Edema; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred C57BL; Passive Cutaneous Anaphylaxis; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Prostaglandin E, EP3 Subtype
PubMed: 16237060
DOI: 10.4049/jimmunol.175.9.5701 -
Acta Oto-laryngologica. Supplementum 1986Light- and electronmicroscopic observations as well as immunohistochemical studies were made on nasal polyps from 15 patients. The patients included 2 cases of aspirin...
Light- and electronmicroscopic observations as well as immunohistochemical studies were made on nasal polyps from 15 patients. The patients included 2 cases of aspirin intolerance (AA), 6 cases of allergic rhinitis (NA) and 7 cases of chronic rhinitis (CS) with negative skin tests against major inhalant allergens. Nasal polyps commonly contained many inflammatory cells such as neutrophils (PMN), eosinophils, plasma cells, mast cells, lymphocytes and macrophages. Two morphological features were conspicuous in our study: 1) PMN migration and attachment to the basal lamina, 2) accelerated degranulation of mast cells. Mean values of degranulated granules were 0.532473/micron2 in AA, 0.492615/micron2 in NA and 0.253591/micron2 in CS. These results indicate that mast cell degranulation in CS is much less than that in AA and NA. Immunohistochemical investigations revealed very few IgE-positive cells in both AA and NA, and none in CS. On the other hand IgG and IgA were frequently observed in all cases of nasal polyps. The present study suggests that mast cell degranulation plays an important role in the formation of nasal polyps, but it may not only be an IgE-dependent mechanism. To elucidate other possibilities, more extensive immunological studies will be required.
Topics: Cytoplasmic Granules; Humans; Immunoenzyme Techniques; Immunoglobulin E; Mast Cells; Microscopy, Electron; Nasal Mucosa; Nasal Polyps; Neutrophils; Nose Neoplasms; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal
PubMed: 3526808
DOI: No ID Found -
International Journal of Food... Jun 2000Histamine (or scombroid) fish poisoning (HFP) is reviewed in a risk-assessment framework in an attempt to arrive at an informed characterisation of risk. Histamine is... (Review)
Review
Histamine (or scombroid) fish poisoning (HFP) is reviewed in a risk-assessment framework in an attempt to arrive at an informed characterisation of risk. Histamine is the main toxin involved in HFP, but the disease is not uncomplicated histamine poisoning. Although it is generally associated with high levels of histamine (> or =50 mg/100 g) in bacterially contaminated fish of particular species, the pathogenesis of HFP has not been clearly elucidated. Various hypotheses have been put forward to explain why histamine consumed in spoiled fish is more toxic than pure histamine taken orally, but none has proved totally satisfactory. Urocanic acid, like histamine, an imidazole compound derived from histidine in spoiling fish, may be the "missing factor" in HFP. cis-Urocanic acid has recently been recognised as a mast cell degranulator, and endogenous histamine from mast cell degranulation may augment the exogenous histamine consumed in spoiled fish. HFP is a mild disease, but is important in relation to food safety and international trade. Consumers are becoming more demanding, and litigation following food poisoning incidents is becoming more common. Producers, distributors and restaurants are increasingly held liable for the quality of the products they handle and sell. Many countries have set guidelines for maximum permitted levels of histamine in fish. However, histamine concentrations within a spoiled fish are extremely variable, as is the threshold toxic dose. Until the identity, levels and potency of possible potentiators and/or mast-cell-degranulating factors are elucidated, it is difficult to establish regulatory limits for histamine in foods on the basis of potential health hazard. Histidine decarboxylating bacteria produce histamine from free histidine in spoiling fish. Although some are present in the normal microbial flora of live fish, most seem to be derived from post-catching contamination on board fishing vessels, at the processing plant or in the distribution system, or in restaurants or homes. The key to keeping bacterial numbers and histamine levels low is the rapid cooling of fish after catching and the maintenance of adequate refrigeration during handling and storage. Despite the huge expansion in trade in recent years, great progress has been made in ensuring the quality and safety of fish products. This is largely the result of the introduction of international standards of food hygiene and the application of risk analysis and hazard analysis and critical control point (HACCP) principles.
Topics: Disease Outbreaks; Fish Products; Food Microbiology; Foodborne Diseases; Histamine; Humans; Marine Toxins; Mast Cells; Risk Factors
PubMed: 10898459
DOI: 10.1016/s0168-1605(00)00296-8 -
International Archives of Allergy and... 1990In the trachea and bronchi of the atropinized rat, the proportion of degranulating mast cells (defined as having one or more granules outside the body of the cell in a...
In the trachea and bronchi of the atropinized rat, the proportion of degranulating mast cells (defined as having one or more granules outside the body of the cell in a 10-microns thick section) was increased from 35-40% to 48-55% following electrical stimulation of one or both vagus nerves for 3 min. The increase occurred bilaterally, though it was greater on the stimulated side. The degranulation of mast cells was prevented by transection of the nerve rostral to the nodose ganglion 8-10 days before stimulation. Pre-treatment of rats with capsaicin also prevented the degranulation of mast cells that otherwise would have followed stimulation of the vagus nerve. These observations indicate that tracheo-bronchial mast cells discharge their granules in response to the activity of capsaicin-sensitive axons of neurons whose cell bodies are rostral to the nodose ganglion. These are probably substance P-containing polymodal nociceptive neurons of the jugular ganglion. If similar neurons exist in man, axon reflexes in their intrabronchial branches would be expected to stimulate the release of mast cell-derived agents that cause bronchoconstriction in asthma.
Topics: Animals; Capsaicin; Cell Degranulation; Electric Stimulation; Lung; Male; Mast Cells; Rats; Rats, Inbred Strains; Trachea; Transcutaneous Electric Nerve Stimulation; Vagus Nerve
PubMed: 2210875
DOI: 10.1159/000235149 -
European Journal of Pharmacology Aug 2010To verify the recently proposed concept that mast cell-derived renin facilitates angiotensin II-induced bronchoconstriction bronchial rings from male Sprague-Dawley rats...
To verify the recently proposed concept that mast cell-derived renin facilitates angiotensin II-induced bronchoconstriction bronchial rings from male Sprague-Dawley rats were mounted in Mulvany myographs, and exposed to the mast cell degranulator compound 48/80 (300 microg/ml), angiotensin I, angiotensin II, bradykinin or serotonin (5-hydroxytryptamine, 5-HT), in the absence or presence of the renin inhibitor aliskiren (10 micromol/l), the ACE inhibitor captopril (10 micromol/l), the angiotensin II type 1 (AT1) receptor blocker irbesartan (1 micromol/l), the mast cell stabilizer cromolyn (0.3 mmol/l), the 5-HT2A/2C receptor antagonist ketanserin (0.1 micromol/l) or the alpha1-adrenoceptor antagonist phentolamine (1 micromol/l). Bath fluid was collected to verify angiotensin generation. Bronchial tissue was homogenized to determine renin, angiotensinogen and serotonin content. Compound 48/80 contracted bronchi to 24+/-4% of the KCl-induced contraction. Ketanserin fully abolished this effect, while cromolyn reduced the contraction to 16+/-5%. Aliskiren, captopril, irbesartan and phentolamine did not affect this response, and the angiotensin I and II levels in the bath fluid after 48/80 exposure were below the detection limit. Angiotensin I and II equipotently contracted bronchi. Captopril shifted the angiotensin I curve approximately 10-fold to the right, whereas irbesartan fully blocked the effect of angiotensin II. Bradykinin-induced constriction was shifted approximately 100-fold to the left with captopril. Serotonin contracted bronchi, and ketanserin fully blocked this effect. Finally, bronchial tissue contained serotonin at micromolar levels, whereas renin and angiotensinogen were undetectable in this preparation. In conclusion, mast cell degranulation results in serotonin-induced bronchoconstriction, and is unlikely to involve renin-induced angiotensin generation.
Topics: Amides; Angiotensinogen; Animals; Biphenyl Compounds; Bronchi; Bronchoconstriction; Captopril; Cell Degranulation; Fumarates; In Vitro Techniques; Irbesartan; Male; Mast Cells; Methacholine Chloride; Rats; Rats, Sprague-Dawley; Renin; Serotonin; Tetrazoles; p-Methoxy-N-methylphenethylamine
PubMed: 20462506
DOI: 10.1016/j.ejphar.2010.04.058 -
FASEB Journal : Official Publication of... Jun 1998Neutrophil degranulation is an important event in inflammatory responses. We examined the regulation of neutrophil (PMN) degranulation by resting and activated human...
Neutrophil degranulation is an important event in inflammatory responses. We examined the regulation of neutrophil (PMN) degranulation by resting and activated human endothelial cells. Whereas PMNs adherent to endothelial cells that were stimulated to express P-selectin and platelet-activating factor did not release the specific granule marker lactoferrin or the primary granule enzyme, elastase, PMNs adherent to endothelial cells stimulated with interleukin-1 (IL-1) or tumor necrosis factor secreted both. PMN degranulation was dependent on the time of incubation of endothelial cells with the cytokine, its concentration, and the time of incubation of the PMNs with endothelial cells. Degranulation of PMNs and their adhesion to stimulated endothelial cells are correlated events, but they could be dissociated by blocking the tethering molecules used by the endothelial cells and neutrophils under these conditions. This suggested that paracrine signaling molecules that induce PMN degranulation are produced by cytokine-stimulated endothelial cells. We found that endothelial cells stimulated with IL-1 release newly synthesized degranulating factors that require transcription and translation. IL-8 was synthesized, released, and signaled granular secretion by PMNs. However, experiments with blocking antibodies indicated the presence of an additional degranulating factor not accounted for by IL-8. These experiments demonstrate that human endothelial cells regulate degranulation of neutrophils by generating signaling factors that are expressed differentially depending on the endothelial agonist and other features. Active modification of neutrophil granular secretion by endothelial cells can influence physiologic acute inflammatory responses but may also contribute to pathologic vascular and tissue damage.
Topics: Cell Adhesion; Cell Degranulation; Cytokines; E-Selectin; Endothelium, Vascular; Humans; Interleukin-1; Interleukin-8; Lactoferrin; Leukocyte Elastase; Neutrophil Activation; P-Selectin; Paracrine Communication
PubMed: 9619452
DOI: 10.1096/fasebj.12.9.733 -
Toxicology and Applied Pharmacology Jan 2018Mast cell (MC) degranulation has been implicated in the side effect profile of a variety of clinically useful agents. Thus, after intrathecal delivery, formation of...
UNLABELLED
Mast cell (MC) degranulation has been implicated in the side effect profile of a variety of clinically useful agents. Thus, after intrathecal delivery, formation of space-occupying, meningeally-derived masses may be related to local MC degranulation. We systematically characterized degranulating effects of opioid and nonopioid analgesics on cutaneous flares in the dog and in primary human MC (hMC) cultures.
METHODS
Dogs were anesthetized with IV propofol and received intradermal (ID) injections (50μL). Flare diameters were measured at 30min. Drugs showing flare responses were tested after intramuscular (IM) cromolyn (10mg/kg), a MC stabilizer. Human primary MCs (human cord blood CD34/CD45 cells) were employed and β-hexosaminidase in cell-free supernatants were measured to assess degranulation.
RESULTS
A significant skin flare for several classes of agents was observed including opioids, ziconotide, ketamine, ST-91, neostigmine, adenosine, bupivacaine, lidocaine, MK-801 and 48/80. Tizanidine, fentanyl, alfentanil, gabapentin and baclofen produced no flare. Flare produced by all ID agents, except adenosine, bupivacaine and lidocaine, was reduced by cromolyn. Naloxone had no effect upon opiate or 48/80 evoked flares. In hMC studies, 48/80 resulted in a concentration-dependent release of β-hexosaminidase. The rank order of drug-induced hMC β-hexosaminidase release was similar to that for flares.
CONCLUSIONS
A variety of therapeutically useful drugs degranulate MCs. This action may account for side effects such as the intrathecal granuloma resulting from spinally-delivered opioids. This degranulating effect may be useful in predicting potential intrathecal toxicity in the development of novel agents.
Topics: Analgesics; Analgesics, Opioid; Animals; Cell Degranulation; Cells, Cultured; Dogs; Humans; Male; Mast Cells; Skin; p-Methoxy-N-methylphenethylamine
PubMed: 29111148
DOI: 10.1016/j.taap.2017.10.017 -
Der Anaesthesist Jan 2009Substantial progress has been achieved in recent years in research on the interaction between pain and pruritus. Over and above the known inhibition of pruritus by... (Review)
Review
Substantial progress has been achieved in recent years in research on the interaction between pain and pruritus. Over and above the known inhibition of pruritus by painful stimuli (e.g. scratching), a foundation for the explanation of opioid-induced pruritus was laid through the discovery of pruritus-specific neuronal processing channels. Although traditionally the degranulating effect of opioids on mast cells was assumed to be the essential mechanism, it is now clear that opioids can also induce itching at the spinal level. Neurons of the dorsal horn of the pain system inhibit spinal itch neurons. If this inhibition is weakened by opioids, the disinhibited itch neurons become active and mediate itching, without stimulation of the primary afferent peripheral nerves. Spinal triggering of itching is observed in particular by activation of mu-opioid receptors (mu-OR), while kappa-OR surprisingly suppress itch. The therapeutic implications of this interaction will be described.
Topics: Analgesics, Opioid; Cell Degranulation; Humans; Mast Cells; Pain; Pruritus; Receptors, Opioid
PubMed: 19132330
DOI: 10.1007/s00101-008-1478-8