Localized mast cell degranulation induced by concanavalin A-sepharose beads. Implications for the Ca2+ hypothesis of stimulus-secretion coupling.

Abstract

Concanavalin A (Con A) covalently linked to Sepharose 4B beads induced localized degranulation of sensitized rat peritoneal mast cells in regions of contact between beads and cells. This degranulation was Ca2+ dependent and was not seen when sensitized mast cells bound to beads conjugated with a nonstimulating lectin, wheat germ agglutinin, or when unsensitized mast cells bound to Con A-Sepharose. The finding that sensitized mast cells which had adhered to Con A-Sepharose beads degranulated in regions of the cell away from the area of bead contact if exposed to soluble Con A excluded the possibility that the localized release was due to a redistribution of the IgE receptors or putative Ca2+ channels to the region of bead contact. The results suggest that, if an influx of Ca2+ is the mechanism for initiating mast cell degranulation, then the opening of Ca2+ channels in the plasma membrane of activated mast cells is a localized event and that Ca2+ acts locally within the cell to initiate exocytosis.

Compound Exocytosis and Cumulative Fusion in Eosinophils

“…It was shown in mast cells that local stimulation induces local degranulation (26). Similarly, stimulation of eosinophils upon contact with a parasite may initiate exocytosis at the site of contact that would then be followed by cumulative fusion leading to focal release.…”

PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis

“…Compound exocytosis is a relatively common mode of exocytosis found in hematopoetic cells such as eosinophils and mast cells (229,332,376). Both VIP activation of adenylyl cyclase and TRH activation of phospholipase C-␤ potentiate compound exocytosis in lactotrophs (112).…”

Differential targeting of secretory lysosomes and recycling endosomes in mast cells revealed by patterned antigen arrays

“…One of the postulated functions of the immunological synapse, the ordered m-scale structure formed at this cell-cell interface is targeted secretion (Stinchcombe et al, 2001). Specific targeting also occurs when antigens are presented on beads (Lawson et al, 1978;Tapper et al, 2002), indicating that intracellular machineries of effector cells alone can achieve this localization. In addition to secretion of soluble mediators, constitutive and stimulated trafficking occurs in cells to maintain or modulate plasma membrane composition.…”