Morphologic Evidence that Compound 48/80-Challenged Rat Eyelid Mast Cells Differ in Their States of Maximal Degranulation

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Abstract
To determine the uniformity of response by mast cells in the rat eyelid, doses of compound 48/80 ranging from 50 to 1,000 μg in a 10-μl drop were applied to one eye of 30 male Sprague-Dawley rats. Phosphate-buffered saline (PBS) was applied to the other eye. Every mast cell was counted throughout microscopic slides of the tissue of the lower eyelids. Both the position and degree of degranulation of every mast cell in each slide were recorded on schematic representations of the lower eyelid. Before histologic examination, animals were observed for clinical signs of ocular anaphylaxis. Doses of 50 and 150 μg had no observable clinical effect. At greater doses, edema of the lids and conjunctiva increased with dose. Doses less than 250 μg had no significant effect on the number of mast cells or degree of degranulation. Doses of more than 250 μg induced degranulation in approximately 50% of the eyelid mast cells. The degree and pattern of degranulation did not change with doses greater than 250 μg. The morphology of degranulated mast cells treated with 1,000 or 250 μg of compound 48/80 was indistinguishable. We conclude that once maximal stimulation for degranulation is achieved, higher levels of compound 48/80 will not increase the level or change the type of degranulation. In addition, the maximal level of degranulation varies from one mast cell to the next. Mast cells in close proximity may differ markedly in their level of maximal degranulation, with responses ranging from no degranulation to severe degranulation with exocytosis.