The mechanism of histamine release from mast cells

Mast cell secretion was studied in vitro using rat peritoneal cells stimulated by polymyxin B sulfate. The dose-response curve for histamine release was only slightly lowered when mast cells isolated by sedimentation through albumin solution (specific gravity, 1.100) were compared to cells not subjected to the isolation procedure. The release of N-acetyl- β-glucosaminidase, a readily soluble component of mast cell granules, closely paralleled the release of histamine. However, little release occurred of two insoluble granule components, mast cell chymase and heparin, and their release was not dose dependent. These results indicated that histamine release from mast cells can occur in the absence of extrusion of their granules. Quantitative studies of the uptake of ruthenium red and morphologic studies of the distribution of ruthenium red and ferritin demonstrated that the granules are effectively extruded into an extracellular space that is confined to the cellular domain by a labyrinth of cytoplasmic processes. The secretory process of mast cells then appears to be effected through a sequence of membrane fusions that produce deep channels of extracellular space penetrating through the cell and enveloping the granules rather than by the propulsion of the granules to the cell surface with extrusion at that site.