Evidence of de novo Membrane Generation in the Mechanism of Mast Cell Secretory Granule Activation

摘要

Overwhelming evidence has suggested that granule matrix swelling and the enlargement of the perigranular membrane are early morphological indicators of mast cell granula activation (1-3). Since excess membrane in the form of folds or inclusions has not been observed in the quiescent granule and it is known that membrane cannot stretch beyond 2-3% of its original area (4), it is necessary to consider that new membrane is generated during granule activation. Fusion of this newly generated membrane with the perigranular membrane would enable the granule to expand and the perigranular membrane to lift from the surface of the granule matrix. By using various ultrastructural techniques, the authors found that: First, rapid-freezing and freeze-substitution of mast cells reveals the presence of membrane vesicles associated with activated or secreted granules. Second, purified granules after removal of their perigranular membrane can generate membrane vesicles. And third, membrane vesicles and the fusion of these vesicles with the perigranular membrane have been observed using a simultaneous activation, fixation, and membrane enhancement (SAFME) procedure. Reprints.