Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis.

BACKGROUND

Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. The role of IgE and mast cells in allergic conjunctivitis is largely unknown, however.

OBJECTIVES

We investigated the importance of conjunctival mast cells in a murine model of IgE-mediated allergic conjunctivitis.

METHODS

IgE-mediated allergic conjunctivitis was initiated in C57BL/6-Kit(+/+) wild-type mice, mast cell-deficient Kit(W-sh/W-sh) mice, and Kit(W-sh/W-sh) mice that had been subconjunctivally or systemically engrafted with bone marrow-derived, cultured mast cells (BMCMCs) from Kit(+/+) wild-type mice, and clinical symptoms and infiltration of eosinophil of the eyes were evaluated. Total numbers of mast cells in the conjunctiva were counted, and the phenotypes of these cells were characterized by means of immunostaining and PCR analysis of murine mast cell proteases.

RESULTS

No mast cells were detected in the conjunctiva or eyelid dermis of adult Kit(W-sh/W-sh) mice. Subconjunctival injection of BMCMCs resulted in local mast cell reconstitution, with the numbers of reconstituted mast cells in the conjunctiva and eyelid dermis comparable with those observed in wild-type Kit(+/+) littermates. Reconstituted and naive conjunctival mast cells expressed proteases ascribed to connective tissue-type mast cells but not mucosal mast cells. Passive transfer of ragweed-specific IgE followed by antigen challenge resulted in both early-phase clinical symptoms and late-phase eosinophilic inflammation in Kit(+/+) mice. These responses, which were significantly decreased in Kit(W-sh/W-sh) mice, were restored on reconstitution of the conjunctival mast cell population.

CONCLUSIONS

These results suggest a direct contribution of IgE-activated mast cells to both the early-phase reaction and late-phase inflammation during ocular allergy.