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)

Immunohistochemical staining of conjunctival biopsies from four normal subjects and five patients with atopic keratoconjunctivitis (AKC) was performed, using a monoclonal antibody to human mast cell tryptase. A massive hyperplasia of mast cells in the patients with AKC was demonstrated. The mean mast cell density in the normal patients was 55.6/mm2 and in the patients with AKC, 172/mm2. The appearance of large numbers of mast cells in the conjunctival epithelium of AKC patients was also demonstrated. The possible pathophysiological significance of these findings is discussed.
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PMID:Mast cell hyperplasia in atopic keratoconjunctivitis. An immunohistochemical study. 180 Jan 75

Conjunctival biopsies from 11 patients with atopic keratoconjunctivitis (AKC) and from 13 age-matched healthy individuals undergoing cataract surgery were analyzed by light microscopy and immunohistochemical techniques. Histology of AKC specimens showed goblet cell proliferation, epithelial pseudotubular formation, eosinophil and mast cell invasion of the epithelium, and pronounced mononuclear cell infiltration of the substantia propria, often with frank granuloma formation. Epithelium of AKC conjunctiva showed significantly more T cells (CD3+, CD5+), T-helper cells (CD4+), macrophages (Mac-1+, CD14+), activated T cells, (CD25+), and dendritic cells (CD1+), and a higher helper/suppressor ratio than did control subjects. In the substantia propria, AKC specimens showed dramatically increased inflammatory cell infiltration with significantly more cells staining, in order of frequency, for T-cells (CD3+, CD5+), T-helper cells (CD4+), T-suppressor/cytotoxic cells (CD8+), macrophages (CD14+, Mac-1+) activated T cells (CD25+), B cells (CD22+), and dendritic cells (CD1+, HLA-DR+). Fifty-three percent of T cells in the substantia propria expressed the interleukin-2 receptor protein (CD25+). These findings indicate that the chronic conjunctivitis of AKC is complex, with activated T-cells and macrophages dramatically participating in the process. Successful long-term control of the potentially binding conjunctival inflammation of this disease is likely to require therapeutic strategies directed toward more than just the mast cell component of the process.
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PMID:Immunopathology of atopic keratoconjunctivitis. 192 55

To investigate the role of the eosinophil in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis, we assessed the presence of eosinophil granule major basic protein in conjunctival tissues by immunofluorescence. Biopsy specimens of conjunctiva were taken from nine patients with vernal keratoconjunctivitis, seven patients with giant papillary conjunctivitis, and five control subjects. We performed a masked semiquantitative assessment of immunofluorescence on sections from each specimen. The vernal keratoconjunctivitis and giant papillary conjunctivitis groups had significantly (P less than .05) more major basic protein deposition than controls. No significant correlation between severity of disease and degree of major basic protein deposition was found. We found extracellular eosinophil granules in one of three vernal keratoconjunctivitis specimens examined by transmission electron microscopy. Thus, eosinophil degranulation commonly occurs in vernal keratoconjunctivitis and giant papillary conjunctivitis with release of eosinophil granule major basic protein and presumably other toxic granule proteins onto affected tissues. These cationic proteins are potent cytotoxins and are able to stimulate mast cell degranulation.
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PMID:Conjunctival deposition of eosinophil granule major basic protein in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis. 275 Aug 34

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

Clinical studies of vernal keratoconjunctivitis (VKC) patients show that total IgE serum levels are increased even in the absence of IgE antibodies to common allergens. Activated eosinophils are also a constant feature of VKC at both the circulation (cytofluorimetry) and tissue (tear cytology and conjunctival scrapings) levels. Moreover, allergen challenge induces a prolonged inflammatory reaction with a prevalent participation of eosinophils, lymphocytes and possibly basophils. Immunohistochemical studies of VKC biopsies show a multicellular inflammatory infiltrate with prevalence of activated eosinophils, mast cells and CD4 lymphocytes in both epithelium and subepithelium. Mediator studies indicate that eosinophil products (eosinophil peroxidase, eosinophinal cationic protein and eosinophil-derived neurotoxin/eosinophil protein X) are increased in both serum and tears, where tryptase and interleukin (IL)-5 are also detectable in higher amounts than in controls. On the basis of these findings, we postulate that VKC can represent a phenotypic model of up-regulation of the cytokine gene cluster on chromosome 5q which through its products (IL-3, IL-4, IL-5 and granulocyte/macrophage-colony-stimulating factor) regulates Th2 prevalence, IgE production as well as mast cell and eosinophil growth and function in VKC.
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PMID:Vernal keratoconjunctivitis: a model of 5q cytokine gene cluster disease. 761 25

Allergic eye disease has a variety of clinical manifestations including seasonal atopic conjunctivitis (SAC), perennial atopic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), and atopic blepharoconjunctivitis (ABC). We have investigated the number, distribution and protease expression of mast cells in normal and diseased conjunctiva with the use of immunohistochemistry in water-miscible resin sections. The median mast cell densities in normal subjects were 17 mm-2 in the bulbar substantia propria and 9 mm-2 in tarsal substantia propria. Mast cells were absent from the normal conjunctival epithelium at both sites. Mast cell densities were increased in the bulbar substantia propria in SAC, AKC and ABC. Tarsal substantia propria showed a significant increase in mast cells in ABC and AKC disease states. Mast cells express a range of proteases which varies according to their anatomic site. Mast cells in connective tissue are described to contain tryptase, chymase, cathepsin-G and carboxypeptidase-A, whereas mucosal mast cells contain only tryptase. In the diseased conjunctiva there was a marked reduction in proteases other than tryptase in the intraepithelial mast cells. There were also significant reductions in protease expression other than tryptase in the bulbar substantia propria in AKC and ABC. There appear to be specific alterations in the distribution of mast cells in the sub-categories of allergic eye disease. The distinction between mucosal and connective tissue mast cell phenotypes is not clear-cut and may depend on the functional state of the mast cells in relation to the microenvironment.
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PMID:Mast cell distribution and neutral protease expression in acute and chronic allergic conjunctivitis. 772 24

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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