The Role of Mast Cells

Mast cell activation results from a multivalent allergen cross-linking cell surface IgE with high affinity FceRI mast cell receptors [9]. Conjunctival mast cell activation leads to the release of histamine and locally synthesized mediators, e.g. prostaglandin D2, leukotriene C4, tryptase, chymase, carboxypeptidase A, cathepsin G, and platelet-activating factor, a powerful eosinophil chemotactic agent and other eosinophil and neutrophil chemoattractants. Allergen challenge in atopic patients leads to an early phase response, which is maximal at 20min, with increased tear levels of histamine, the mast cell protease tryptase, leukotrienes and eosinophils [10].

At 6 h there is a dose-dependent late phase response, with a second peak in tear concentrations of histamine and eosinophil cationic protein levels. Tryptase is not increased, suggesting that either mast cells are still degranulated, or that other cells such as basophils, whose conjunctival numbers are increased at this stage, are involved. The tissue adhesion molecules E-selectin and ICAM-1, but not VCAM-1, are increased at 6 h consistent with the increased conjunctival levels of granulocytes and eosinophils [11]. IgE is produced in the conjunctiva, under mast cell control, and most patients with allergic eye disease have a positive family history of atopy with raised serum and tear levels of allergen-specific IgE. Mast cells induce B cell IgE production independently of T cells, suggesting that mast cells may be involved in the autoregulation of IgE production through the CD40/CD40 ligand [12].

The clinical effectiveness of the histamine H1 receptor antagonist emedastine supports the involvement of mast cells in allergic eye responses; emedastine potently inhibited histamine-induced secretion of interleukin (IL)-6, IL-8 and granulocyte-macrophage colony-stimulating factor, as well as the topical mast cell stabilizers, e.g. sodium cromoglycate, lodoxamide [13, 14] and nedocromil [15], which reduce tear concentrations of tryptase. Topically applied antihistamines (e.g. levocabastine [16]) and systemic histamine H1 receptor antagonists (e.g. astemizole, terfenadine and loratadine) are also effective in the treatment of SAC and PAC [17].

Mast cell release of histamine and leukotrienes contributes to the inflammatory response by the recruitment of eosinophils and neutrophils. Eosinophil numbers are also increased in the chronic forms of allergic eye disease [18]. In AKC and VKC, they are not only increased in the deep layers of the conjunctiva (lamina propria) but also migrate into the epithelium [19]. In VKC, there are increased tear levels of eosinophil cationic protein, eosinophil granule major basic protein and Charcot-Leyden crystal protein. Eosinophil granule-derived proteins have been localized to the base of vernal ulcers [20]. Neutrophil numbers are also increased in the conjunctiva of atopic subjects after allergen challenge [17]. Histamine, through H1 receptors in the conjunctiva, appears to couple to inositol phosphate, increasing intracellular calcium, and results in the development of pruritus. Histamine stimulation of H2 receptors on the ocular surface causes vasodilation [11].

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