Conjunctival mast cell as a mediator of eosinophilic response in ocular allergy
ABSTRACT To determine the contribution of conjunctival mast cells to the allergen-specific inflammatory responses in eyes with allergic conjunctivitis and to test the hypothesis that mast cells act as mediators of the early phase response.
The participation of mast cells in allergen-induced inflammatory cell recruitment was studied in an experimental murine model of allergic conjunctivitis. Experimental allergic conjunctivitis was induced by a single or multiple sensitizing injections of an allergen. The conjunctiva of allergen-sensitized, mast cell-deficient (Kit(w)/Kit(w-v)) mice were reconstituted with conjunctival mast cells isolated from naïve wild type mice by subconjunctival transfer. Kit(w)/Kit(w-v) mice and conjunctival mast cell reconstituted Kit(w)/Kit(w-v) mice were evaluated for early phase reactions and late phase inflammatory responses.
The early phase response was minimal in Kit(w)/Kit(w-v) mice after both a single injection and multiple sensitization injections of the allergen. The early phase responses were fully restored following adoptive transfer of isolated conjunctival mast cells from naïve wild type mice. Eosinophilic inflammatory responses were significantly depressed in Kit(w)/Kit(w-v) mice without the impairment of allergen-specific priming. Reconstitution of the conjunctiva of Kit(w)/Kit(w-v) mice with mast cells from wild type mice fully restored the allergen-specific eosinophilic responses but not the neutrophilic responses.
Our data indicate that conjunctival mast cells are essential for eosinophilic inflammation but not for neutrophilia in allergic conjunctivitis that is mediated by mast cell activation.
SourceAvailable from: Alexander N Shikov[Show abstract] [Hide abstract]
ABSTRACT: This study was undertaken to evaluate possible antiallergic effects of an extract of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells. Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes allergic conjunctivitis, and rabbit local skin irritation. The extract significantly reduced, in a dose-dependent manner, the histamine-induced contractions of the isolated guinea pig ileum with ID50 = 1.2 µg/mL (in equivalents of spinochrome B), had an inhibitory effect on the model of ocular allergic inflammation surpassing the reference drug olopatadine, and did not show any irritating effect in rabbits. The extract predominantly contained polyhydroxy-1,4-naphthoquinone which would be responsible for the pharmacological activity. The active compounds of the extract were evaluated in silico with molecular docking. Molecular docking into H1R receptor structures obtained from molecular dynamic simulations showed that all spinochrome derivatives bind to the receptor active site, but spinochrome monomers fit better to it. The results of the present study suggest possibilities for the development of new agents for treating allergic diseases on the base of pigments from sea urchins shells.Planta Medica 11/2013; 79(18). DOI:10.1055/s-0033-1351098 · 2.34 Impact Factor
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ABSTRACT: The aim of the present investigation is to study the effects of topical ocular montelukast in an animal model of allergic conjunctivitis in rabbits. Eighteen Albino New Zeeland rabbits were used and divided into six groups; three of which served as controls. Allergic conjunctivitis model was induced in the other three groups (IV, V and VI) by topical application of 1000 µg of compound 48/80 in each eye. Group IV was left untreated while groups V and VI were treated with 0.1% montelukast and 1% prednisolone eye drops respectively. The eye drops were applied before application of the compound. The eyes were evaluated by clinical examination and scoring of the allergic manifestations as well as by light microscopic examination of the conjunctiva. Both montelukast and prednisolone produced improvement of the allergic manifestations detected both clinically and histologically with prednisolone being more effective than montelukast. In conclusion, topical ocular montelukast can be a potential therapeutic drug with a new route of administration that can be used for treatment of allergic conjunctivitis.
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ABSTRACT: Introduction: Allergic conjunctivitis (AC) is a very common disease, especially in association with allergic rhinitis but may also occur in isolated presentation. The treatment of AC has long been based on antihistamines, cromones and topical corticosteroids, but none of these drugs completely abolishes the clinical expression of AC. Areas covered: The development of new drugs for AC is analyzed highlighting the recent insights into the pathophysiological mechanisms of the disease. The major aim of development of drugs for AC is to have agents able to prevent the inflammatory effects of the interaction between the allergen and the specific IgE antibodies on mast cell surface. This may be obtained by blocking the effects of histamine (the main mediator of early allergic response) by H1-receptor antagonists, inhibiting the release of soluble factors able to recruit inflammatory cells (that sustain prolonged inflammation) by mast-cell stabilizers, inhibiting the effects of single mediators, inducing tolerance to the allergen by specific immunotherapy or even acting on factors related to activation and differentiation of T lymphocytes such as the toll-like receptors. Expert opinion: AC is an underestimated disease for which there is a search of more effective treatments. The availability of the drugs under current evaluation will allow more refined therapeutic strategies to apply according to the characteristics and the clinical severity of AC.Expert Opinion on Emerging Drugs 03/2014; 19(2). DOI:10.1517/14728214.2014.902443 · 3.28 Impact Factor