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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the release of histamine, a major mast cell mediator of conjunctival type I reactions, and the production of a prostanoid, prostacyclin (prostaglandin I2, PGI2), was examined in a guinea pig model of allergic conjunctivitis. Guinea pigs were sensitized topically and challenged by repeated conjunctival instillation of fluoresceinyl ovalbumin. Histamine and 6-keto-PGF1 alpha, the stable product of the spontaneous degradation of PGI2, were measured in tears by radioimmunoassays. Clinical type I reactions and tear histamine appeared by 8 days and increased up to 22 days during the initial sensitization, with notable variations between animals. The kinetics of histamine and 6-keto-PGF1 alpha release in tears were examined over a 24-hr period after the antigen challenge. Histamine release was maximal during the first 10 min and returned to baseline values by 1 hr in all instances. The 6-keto-PGF1 alpha release also peaked during the first 10 min but continued for an extended period. The ratio of tear 6-keto-PGF1 alpha to histamine increased more than 16-fold over the 2 hr after antigen challenge. Late-phase reactions with second peaks of histamine or 6-keto-PGF1 alpha in the tears were observed in two different guinea pigs 4-8 hr after antigen challenge. Histamine applied to the eyes of naive guinea pigs also induced the release of 6-keto-PGF1 alpha in tears. Histamine appeared to act as a primary mediator, stimulating the secondary production and release of PGI2 by constitutive (eg, vascular) and possibly infiltrating inflammatory cells during an allergic conjunctival reaction.
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PMID:Histamine and prostacyclin. Primary and secondary release in allergic conjunctivitis. 171 64

The presence of eosinophils in the conjunctival epithelium is indicative of allergies, and detection is currently performed by cotton swab scrapings. Although mast cells are thought to be chemotactic for eosinophils and thus presage their accumulation, the former's use as early indicators of allergy has heretofore been hindered by poor detection methods. The recent development of a special brush now makes it possible to collect many cells with less disturbance of the conjunctival epithelium. In the present study, we have used this brush for conjunctival scraping in 18 patients with vernal and allergic conjunctivitis, and 10 patients serving as controls. The superior and inferior tarsal conjunctiva in both eyes were examined, and the specimens were stained using Hansel's method. Mast cells were observed in at least one of the tarsal conjunctivae in all cases of vernal and allergic conjunctivitis, whereas eosinophils were so observed in only eight cases (44.4%). Neither mast cells nor eosinophils were present in the conjunctivae of the normal group. Although treatment by mast cell stabilizers produced clinical remissions, they induced disappearance of mast cells in only 10 cases (55.6%), whereas in six cases (33.3%) the mast cells increased, and in two cases they were unchanged (11.1%). Six cases (33.3%) each showed disappearance of, increase in, and no change in eosinophils, reflecting even less of a response of these allergic cells to the treatment. The presence of mast cells and eosinophils, as determined by our cytologic method, was found to be correlated with the early detection, but not the clinical severity, of allergic conjunctivitis.
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PMID:Detection by brush cytology of mast cells and eosinophils in allergic and vernal conjunctivitis. 178 81

Tryptase, a neutral endoprotease, is secreted by activated mast cells in human tissues. Tryptase levels in various body fluids have been used as an indicator of mast cell activation. The authors determined tryptase levels in unstimulated tears collected from the following groups of patients: (1) normal control, (2) nonallergic ocular inflammation, (3) asymptomatic seasonal allergic conjunctivitis, (4) symptomatic seasonal allergic conjunctivitis, (5) vernal conjunctivitis, and (6) contact lens-associated giant papillary conjunctivitis. They also assessed the release of tryptase into the tear fluid after provoking the conjunctiva with (7) allergens, (8) compound 48/80, and (9) rubbing. Tryptase levels were elevated in tears of patients with active ocular allergy and also increased after provoking the conjunctiva with allergens in atopic subjects and with compound 48/80 and rubbing in nonatopic subjects. Tryptase levels in tear fluid may prove useful as a clinical indicator of mast cell involvement in ocular allergic disorders. In provocation experiments, tryptase levels may be used to evaluate and compare different mast cell stabilizing agents.
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PMID:The level of tryptase in human tears. An indicator of activation of conjunctival mast cells. 208 98

In the present study we sought to develop a model of ocular anaphylaxis based on the topical application of compound 48/80 to the surface of the rat eye. Doses ranging from 50 to 1000 micrograms were found to produce graded edema of the conjunctiva and swelling of the lid. On histologic examination, 50 microns compound 48/80 produced no changes distinguishable from those in PBS-treated controls, 150 microns produced mild alterations, and 250, 500, and 1000 micrograms compound 48/80 produced a marked increase in degranulated mast cells and a mild influx of neutrophils. The time course of the response to 250 micrograms and 1000 micrograms of compound 48/80 was evaluated over a 72-h period. Both doses elicited epithelial damage. A mild reduction in the number of mast cell was seen at 6 h in rats receiving 250 or 1000 micrograms. The reduction persisted to 72 h in rats receiving 1000 micrograms. The number of neutrophils was increased at 1 and 6 h in eyes treated with 250 micrograms and at 1, 6, and 24 h in eyes treated with 1000 micrograms compound 48/80. The clinical and histologic changes induced by application of 250 micrograms compound 48/80 resemble those seen in patients with allergic conjunctivitis suggesting that a model of ocular anaphylaxis based on the topical application compound 48/80 will be clinically relevant and experimentally practical.
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PMID:Ocular anaphylaxis induced in the rat by topical application of compound 48/80. Dose response and time course study. 255 44

Sodium cromoglycate stabilizes mast cell membranes and prevents the release of histamine and other biochemical mediators. When topically applied to the eye before allergen exposure, ocular sodium cromoglycate prevents many of the signs and symptoms associated with type I allergic reactions (which includes hayfever, acute allergic and chronic allergic conjunctivitis, and vernal keratoconjunctivitis) and giant papillary conjunctivitis. Although difficulties exist in evaluating clinical trials in allergic eye disease, both open and controlled studies have shown ocular sodium cromoglycate to be very effective in relieving the subjective symptoms and clinical signs of the above ocular disorders. In addition, ocular sodium cromoglycate may decrease the need for supplementary oral antihistamines and, more importantly, the need for ocular corticosteroids, thus decreasing the incidence of steroid-induced ocular side effects. However, in severe cases and in instances of acute exacerbation of symptoms, the combined ocular application of sodium cromoglycate and corticosteroids may be very effective. No systemic or severe adverse reactions have been attributed to ocular sodium cromoglycate, which is not surprising since systemic drug absorption from the eye is minimal. However, transient local stinging and burning have been reported. Thus, although further studies in giant papillary conjunctivitis and comparative studies with corticosteroids in allergic conjunctivitis and vernal keratoconjunctivitis are needed to more clearly define the extent of benefits that may be obtained from ocular sodium cromoglycate, it is clear that the safety and efficacy of the drug in type I allergic eye diseases is such that it should be considered as a first-line agent when drug therapy of these disorders is indicated.
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PMID:Ocular sodium cromoglycate. An overview of its therapeutic efficacy in allergic eye disease. 308 17

The role of the mast cell in ocular allergy is becoming understood. As a result, the therapeutic effects of agents that stabilize the mast cell have been evaluated in the treatment of seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis. At present, cromolyn sodium is the only available mast cell stabilizer of known effectiveness. Clinical and laboratory investigations of the effectiveness of cromolyn sodium in the treatment of ocular allergy are reviewed in the present article.
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PMID:Ocular allergy and mast cell stabilizers. 308 25

Disodium cromoglycate has recently been approved for ophthalmic treatment of certain types of conjunctivitis in the United States. This mast cell inhibitor is effective in the treatment of vernal keratoconjunctivitis, allergic conjunctivitis, chronic conjunctivitis, and giant papillary conjunctivitis, especially when a history of atopic disorders or moderately low blood IgE levels are present. This literature review provides a foundation for understanding the balance between the therapeutic efficacy, clinical benefits and side effects in treating IgE-mediated conjunctivitis with disodium cromoglycate.
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PMID:Ophthalmic disodium cromoglycate. 393 47

Immuno-histopathological studies of conjunctival tissue biopsied from patients with non-sight-threatening allergic conjunctivitis or with sight-threatening allergic keratoconjunctivitis should lead to more effective management of these eye conditions, based on the specific cellular involvement. The major difference between these two categories of eye disease was the occurrence of T-lymphocytes, which were absent in the former but prominent in the sight-threatening disorders. Seasonal and perennial allergic conjunctivitis both showed a heavy mast cell increase, due to infiltration of mucosal type mast cells, and allergen challenge studies linked mast cell histamine release to the early phase reaction occurring within 20 minutes. A second histamine peak at six hours after challenge might implicate basophils (or refractory mast cells) and was accompanied by a rise in eosinophil cationic protein. In sight-threatening, chronic allergic keratoconjunctivitis the responses were clearly directed by T-cells, themselves the primary effector cell in atopic keratoconjunctivitis, whereas vernal keratoconjunctivitis displayed a T-cell driven eosinophilia, with increased expression of the adhesion molecules involved in tissue invasion by these cells. Appropriate therapies for each different category of conjunctivitis should be based on the specific immunopathology, and directed at the activated cell types that are primarily responsible for the disease process.
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PMID:Therapeutic considerations: symptoms, cells and mediators. 754 Mar 64

In a primary healthcare facility, there are certain 'rules of thumb' that can be recommended for the diagnosis and treatment of conjunctivitis. The type of discharge is a crucial factor in the differential diagnosis and can also be a clue towards the management in primary care. It is important to identify whether the conjunctivitis is an isolated case or part of another disease, and if it is acute or chronic, and I would suggest taking a smear or culture sample whenever possible. When the aetiology is not clear, I would try antibiotics. If the patient is allergic, and an allergic conjunctivitis is suspected, the best management today is to use mast cell stabilisers, and combine these with conservative measures of frequent washings, and compresses. If the aetiology remains doubtful, or if there is no obvious improvement using these treatments, the patient should be re-evaluated and/or referred to an ophthalmologist or specialist eye centre. The use of corticosteroids for conjunctivitis should certainly be avoided in primary healthcare. Conjunctivitis is often self-limited and the drug-induced consequences of improper management can be far more devastating than the disease itself.
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PMID:Current practice: diagnosis and treatment in primary healthcare. 778 48

Seasonal allergic conjunctivitis is the only ocular disease to involve solely Type-1 hypersensitivity, the other main forms of ocular allergy--perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis--each having a more complex immunological basis and a chronic inflammatory component. Involvement of secondary inflammatory cells, particularly eosinophils, in addition to the mast cells resident in the conjunctival substantia propria, can lead to more serious corneal damage with vision-threatening potential. Thoughtful management of allergic conjunctivitis is needed in order to control the ocular inflammation without incurring steroid-induced side-effects, and patient education is also an important factor in maintaining optimal allergen avoidance, especially in the more severe and chronic cases. Laboratory models can be helpful in assessing the potential of new drugs, and SWR mice (topically sensitised and challenged with short ragweed) show clinical signs of allergic conjunctivitis, together with mast cell and eosinophil involvement, remarkably similar to the human pathophysiology. The antiinflammatory activity of both steroids and nedocromil sodium observed in this animal model supports therapeutic evidence of the usefulness of second-generation mast cell stabilising drugs in the treatment of ocular allergy.
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PMID:The pathophysiology of ocular allergy: current thinking. 778 49


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