Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study has been to determine whether the presence of lymphocytic infiltrates observed in the histology of ocular allergic conditions in humans or in the late phase of ocular anaphylactic reactions in experimental animals is a non-specific event dependent only on the degranulation of mast cells, or is conditioned by a specific response to antigen. With this in mind, responses to antigen and to a non-immunological mast cell degranulator (compound 48/80) were compared in an experimental model of allergic conjunctivitis. Rats were sensitised to ovalbumin and challenged topically in the left conjunctival sac either with ovalbumin or compound 48/80. The presence of T cells and activated T cells in the infiltrate was studied by immunohistochemical staining on conjunctival tissue obtained at 4, 24, and 48 hours after challenge. Ovalbumin sensitised and challenged rats showed increased numbers of T cells in the conjunctival infiltrate, statistically significant when compared with compound 48/80 challenged rats at 48 hours and with controls at 4, 24, and 48 hours. The number of T cells was significantly higher in compound 48/80 challenged rats only at 48 hours when compared with controls. As for the number of activated T cells, only ovalbumin sensitised and challenged rats showed significantly increased levels of these cells compared with both sensitised animals challenged with compound 48/80 and controls at 4 and 24 hours after challenge. These results suggest that the infiltration of the conjunctiva by activated T lymphocytes is, at least in part, dependent on a specific response to antigen.
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PMID:Activated T cells in an animal model of allergic conjunctivitis. 802 49

We evaluated the pharmacodynamic and pharmacokinetic profile of Mipragoside, a monosialoganglioside isopropyl-ester (as 0.5% w/w ophthalmic gel), on allergic inflammation of the eye induced by reverse passive Arthus reaction, on a non-immune mast cell degranulation elicited by compound 48/80 and on ocular inflammation produced by horse serum. Conjunctiva was sensitized by injection of rabbit antisera to bovine proteins and the allergic conjunctivitis was triggered by intravenous administration of bovine gamma globulin. The permeability of the blood-conjunctival barrier was evaluated by a fluorometric method. Compound 48/80 was topically administered at concentration of 50mg/ml and histological analysis of conjunctiva was performed. Horse serum was administered by intravenous injection at different days. The pharmacokinetic profile of topical 3H-Mipragoside on 48/80 model was investigated and compared with untreated animals. Mipragoside treatment significantly reduced (p < 0.05 vs placebo) the conjunctival vasopermeability induced by reverse passive Arthus reaction as well as successfully reduced the eosinophil levels in the conjunctival epithelium (p < 0.01 vs placebo) elicited by compound 48/80. Further, Mipragoside successfully reduced the primary signs of ocular inflammation produced by horse serum administration. A radiotracer technique was used to evaluate the disposition of 3H-Mipragoside in the rabbit ocular tissues. Disposition of the drug was monitored at 30, 60, 120 and 240 min. 3H-Mipragoside levels in the inflamed conjunctiva were significantly higher (p < 0.01) than in the control eye.
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PMID:Effects of Mipragoside on ocular allergic inflammation in the rabbit. 810 38

In this immunohistochemical light microscopic study we applied a panel of monoclonal antibodies to study the expression pattern of adhesion molecules in normal human conjunctiva from 15 patients. The molecules we analyzed included the VLA-family VLA-1-6, the leukocyte integrins LFA-1, Mac-1 and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectin ELAM-1. Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-alpha 6 subunit are expressed on the epithelium. A strongly basal accentuation of the VLA-alpha 6 subunit indicates its possible relevance in anchoring the epithelium at the substantia propria. Intraepithelial T cells were VLA-1, VLA-5, LFA-1, and CD2 positive. Endothelial cells expressed VLA-1, VLA-2, VLA-3, VLA-5, VLA-alpha 6, ICAM-1, and LFA-3. ELAM-1 was seen only in specimens from five patients. Interestingly, mast cells were positive for VLA-3 and VLA-5, both of which are receptors for fibronectin, indicating that these integrins play an important role in mast cell function. Our study builds the basis for further investigations in adhesion molecules in conjunctival diseases.
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PMID:Adhesion molecules in normal human conjunctiva. An immunohistological study using monoclonal antibodies. 833 47

The term ocular allergy encompasses a group of diseases in which there is a high frequency of atopy, ocular itching, stringy discharge and a papillary conjunctival reaction. Conditions confined to the lids and conjunctiva (e.g. seasonal allergic conjunctivitis) have a good prognosis but those involving the cornea may result in visual impairment (e.g. atopic keratoconjunctivitis). Mast cell and eosinophil mechanisms are important in al the ocular allergies, but T cell inflammation is prominent only in vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Therapy involves the use of antigen avoidance (where possible), nonspecific medical therapy (e.g. cold compresses, artificial tears), specific medical therapy and, in certain situations, immunotherapy and surgery. Topical antihistamines (often in combination with a vasoconstrictor) and oral antihistamines are widely used in perennial and seasonal conjunctivitis. Levocabastine is a new preparation which is more rapid and potent. Mast cell inhibitors [e.g. sodium cromoglycate (cromolyn sodium)] have a proven track record as safe and effective therapy for all ocular allergic diseases and the newer, more potent nedocromil and lodoxamide are now available. Topical steroids are only indicated in sight-threatening disease due to their serious adverse effects and other therapy should be continued to minimise the dose required. There is a lack of intermediate potency and high potency but safe topical preparations. A number of future possibilities exist, some of which have been partially explored. Cyclo-oxygenase inhibitors have proved of limited use, but inhibitors of lipoxygenase and kinin pathways are awaited. Although results with HEPP have been disappointing, other modulators of mast cell function (e.g. picumast, beta-agonists and phosphodiesterase inhibitors) may prove useful in the future. So far, results with topical cyclosporin in serious disease are very encouraging. Future developments in the manipulation of eosinophilic products, cytokines and adhesion molecules may also be relevant. However, the current situation for those with serious ocular allergy remains a disturbing dependence upon topical steroids, with all the attendant risks.
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PMID:Therapeutic options in ocular allergic disease. 852 55

Mast cells are crucial components of immediate and some delayed-type hypersensitivity reactions. They play a pivotal role in allergic conjunctivitis and other immunoinflammatory disorders of the ocular surface, yet little is known of their distribution and heterogeneity in the conjunctiva of potential animal models, such as the rat. In this study, mast cell types were investigated in histologic sections and corneal-conjunctival-lid whole mounts by using toluidine blue, alcian blue-safranin, and immunohistochemical staining methods (anti-rat mast cell proteinase [RMCP] antibodies). Quantitative analyses were performed on corneal-conjunctival-lid whole mounts by using the optical dissector procedure to obtain the density of mast cells per unit volume in different regions of the conjunctiva. Single and double immunohistochemical analyses revealed that the mast cells in the conjunctiva of the limbus, fornices, and lid margin were strongly RMCP I+, suggesting that they were of the connective tissue phenotype. Mast cells containing the mucosal mast cell proteinase RMCP II were not present in the normal conjunctiva. Histochemical analysis revealed that the maturity of the connective tissue mast cells, as assessed by the presence or absence of safranin (heparin)-positive granules in their cytoplasm varied in different regions. In the lid margin 60% to 78% of the mast cells were solely alcian blue-positive, whereas in the fornices 68% to 78% were safranin-positive. In the limbus the predominant type of mast cell was either safranin-positive or contained mixed granules. Mast cell densities were greatest close to the lid margin (10,000 to 12,000 cells/mm3), followed by the limbus (3400 to 4800 cells/mm3) and were rare in the remainder of the conjunctiva (500 to 1000 cells/mm3), with the exception of the region around the nictitating membrane. This study of rat conjunctival mast cells provides essential baseline data for future studies of the role of mast cells in models of allergic conjunctivitis.
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PMID:Immunomorphologic studies of mast cell heterogeneity, location, and distribution in the rat conjunctiva. 864 35

Olopatadine (AL-4943A; KW-4679) [(z)-11-[3-(dimethylamino)propylidene]-6, 11-dihydrodibenz[b,e]oxepine-2 acetic acid hydrochloride] is an anti-allergic agent which inhibits mast cell mediator release and possesses histamine H1 receptor antagonist activity. Studies were conducted to characterize the in vitro and in vivo pharmacological profile of this drug relevant to its topical ocular use. AL-4943A inhibits histamine release in a concentration-dependent fashion (IC50 = 559 microM) from human conjunctival mast cell preparations in vitro. Histamine release was not stimulated by AL-4943A at concentrations as high as 10 mM. In contrast, ketotifen stimulated histamine release at concentrations slightly higher than effective inhibitory concentrations. AL-4943A did not display any in vitro cyclooxygenase or 5-lipoxygenase inhibition. Topical ocular application of AL-4943A effectively inhibits antigen- and histamine-stimulated conjunctivitis in guinea pigs. Passive anaphylaxis in guinea pig conjunctiva was attenuated by AL-4943A applied 30 min prior to intravenous or topical ocular antigen challenge (ED50 values 0.0067% and 0.0170%, w/v, respectively). Antihistaminic activity in vivo was demonstrated using a model of histamine-induced vascular permeability in guinea pig conjunctiva. AL-4943A applied topically from 5 min to 24 hrs prior to histamine challenge effectively and concentration-dependently inhibited the vascular permeability response, indicating the compound has an acceptable onset and a long duration of action. Drug concentrations 5-fold greater than those effective against histamine-stimulated conjunctival responses failed to inhibit vascular permeability responses induced with either serotonin or Platelet-Activating-Factor. These data indicate that the anti-histaminic effect observed with AL-4943A is specific. These anti-allergic/antihistaminic activities of AL-4943A observed in preclinical model systems have been confirmed in clinical trials in allergic patients.
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PMID:The in vitro and in vivo ocular pharmacology of olopatadine (AL-4943A), an effective anti-allergic/antihistaminic agent. 895 75

We sought to establish and immunocytochemically characterize primary cultures of human conjunctival epithelial (HCE) cells, and to determine the types of receptors coupled to adenylate cyclase (AC) and phospholipase C (PLC) present on them which may be stimulated following allergic or inflammatory provocation of the tissue. HCE cells possessed the key epithelial cell surface cytokeratins AE1, AE3 and AE5. Signal transduction studies (n > or = 3), using agonists and antagonists, revealed the presence of beta 2-adrenergic (isoproterenol EC50 = 5.2 nM), prostaglandin E2 (EC50 = 168 nM) and vasoactive intestinal peptide (EC50 = 0.69 nM) receptors positively coupled to AC in HCE cells. Bradykinin (EC50 = 0.83 nM), platelet activating factor (EC50 = 4.5 nM), leukotriene C4 (EC50 = 300 nM) and histamine1 (EC50 = 3.1 microM) receptors were coupled to PLC (n = 3 for each). These data suggest that HCE cells in vivo may represent target cells for mast cell mediators and certain neurotransmitters which are released into the tear-film upon allergic provocation of the conjunctiva.
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PMID:Pharmacological analysis of mast cell mediator and neurotransmitter receptors coupled to adenylate cyclase and phospholipase C on immunocytochemically-defined human conjunctival epithelial cells. 926 68

We examined the number and phenotype of mast cells, and the localization of stem cell factor (SCF) as a growth factor of mast cells in the excised tissue of 38 cases of pterygium. In histopathology with toluidine blue stain and immunohistochemistry with a monoclonal antibody to tryptase, the mean mast cell count in pterygium specimens was twice as high as in normal conjunctiva. In pterygium specimens more than 94% of tryptase-positive mast cells were found to express chymase and c-kit. There was no phenotypic difference between mast cells in pterygium and normal conjunctiva. In all immunohistochemical specimens in which we could examine the head of the pterygium, SCF was expressed in subepithelial fibroblasts at the central edge of pterygium. The results suggest that overexpression of SCF was accompanied with the augmentation of mast cells in the pterygium.
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PMID:[Pterygium and mast cells--mast cell number, phenotype, and localization of stem cell factor]. 928 22

We examined the expression of basic fibroblast growth factor (bFGF) protein immunohistochemically, and bFGF specific messenger RNA (bFGF-mRNA) by in situ hybridization in the excised tissue of 5 cases of pterygium and 4 cases of normal conjunctiva. Immunohistochemical staining for bFGF showed strong positive staining in metachromatic mast cells stained with toluidine blue in the pterygium and in normal conjunctival specimens. The mean metachromatic mast cell count in pterygium specimens was increased significantly when compared with normal conjunctiva. In mast cells, bFGF positive rate was 84% in pterygium specimens, and 69% in normal conjunctival specimens. In situ hybridization indicated that the bFGFmRNA is located in most mast cells in pterygium specimens, but in only a few mast cells in normal conjunctival specimens. These results suggest that increased bFGF protein produced and stored by mast cells in the pterygium may contribute to its progression.
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PMID:[Pterygium and mast cells--expression of basic fibroblast growth factor increase in mast cells of the pterygium]. 961 21

The aim of this study was morphological analysis of corneal disks and conjunctival biopsy specimens in order to disclose the mechanisms of development of epithelial-endothelial dystrophy (EED) and validating pathogenetically-based therapy. Twenty-five patients were observed, 11 of these with implanted intraocular lenses of different localization. EED developed for 1 to 5 years. Sixteen biopsy specimens of the conjunctiva and 21 corneal disks were examined. The composition and index of inflammatory infiltrate, status and compactness of conjunctival vessels, severity of fibrosis, and mast cell degranulation were assessed. Mast cells play a positive role at the initial stages of tissue and cellular response to injury by regulating the formation of extracellular matrix and fibroblast proliferation. At the reparative stages of immune inflammation of the conjunctiva, mast cells are virtually the only cell population; fibrosis and sclerosis develop when the capillary bed is reduced, causing ischemic involvement of the anterior segment of the eye and dystrophic processes in the cornea. A differentiated approach to treatment of EED at the stages of immune inflammation and fibrosis is emphasized.
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PMID:[Morphogenesis of corneal epithelial-endothelial dystrophy (a comparative morphological analysis of corneal disks and biopsy specimens of the conjunctiva)]. 962 23


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