Connective tissue mast cells exhibit time-dependent degranulation heterogeneity

Previous studies have identified two ultrastructurally distinct forms of mast cell (MC) degranulation following activation. Immunoglobulin E (IgE)-mediated reactions are characterized by a very rapid swelling and fusion of MC granules and abrupt mediator release. In certain chronic disease states (e.g., bullous pemphigoid), there is "piecemeal" degranulation with a more-gradual mediator release effected by microvesicular transport of "pieces" of granules to the cell surface. It is unclear whether these two degranulation patterns are determined by the different natures of the stimuli, heterogeneity among responding MC granules, or temporal factors. To investigate these issues, we have carried out electron microscopic studies with skin biopsies obtained from ragweed-sensitive subjects 15 and 30 s and 1, 3, 5, and 10 min after intradermal ragweed injection. "Anaphylactic"-type granule changes began by 15 s after ragweed injection and were complete by 5 min; unaffected granules were juxtaposed with granules that were swollen and fused. The remaining granules subsequently underwent changes in appearance similar to those seen in piecemeal degranulation. However, microvesicular transport of granule components to the surface was not observed. These findings indicate that skin MC changes in sites of IgE-mediated reactions include not only the typical very rapid anaphylactic degranulation but also a slower onset of gradual alteration of other granules, frequently within the same MC. These different patterns could reflect MC granule heterogeneity with attendant different responses to IgE-mediated stimuli.