Sequential Exocytosis of Storage Granules during Antigen‐Induced Histamine Release from Sensitized Rat Mast Cells in vitro An electron microscopic study

Anderson, Per; Slorach, S. A.; Uvnäs, Börje

doi:10.1111/j.1748-1716.1973.tb05465.x

Cited by 97 publications

(52 citation statements)

References 16 publications

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“…Early in the secretory process, single granules fuse with the plasma membrane, whereas at later stages membranes of adjacent granules in the cell interior fuse in succession to produce deep invaginations in the cell surface (1,19,28). These morphological observations correlate well with chemical measurements of release showing that 40-80% of the total cell histamine is secreted within 2 min (3,28).…”

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confidence: 71%

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Arrest of membrane fusion events in mast cells by quick-freezing.

Chandler¹,

Heuser

1980

The Journal of Cell Biology

238

122

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We have used quick-freezing and freeze-fracture to study early stages of exocytosis in rat peritoneal mast cells. Mast cells briefly stimulated with 48/80 (a synthetic polycation and well-known histamine-releasing agent) at 22°C displayed single, narrow-necked pores (some as small as 0.05 pm in diameter) joining single granules with the plasma membrane . Pores that had become as large as 0.1 lm in diameter were clearly etchable and thus represented aqueous channels connecting the granule interior with the extracellular space. Granules exhibiting pores usually did not have wide areas of contact with the plasma membrane, and clearings of intramembrane particles, seen in chemically fixed mast cells undergoing exocytosis, were not present on either plasma or granule membranes. Fusion of interior granules later in the secretory process also appeared to involve pores; granules were often joined by one pore or a group of 2-4 pores . Also found were groups of extremely small, etchable pores on granule membranes that may represent the earliest aqueous communication between fusing granules .Ultrastructural studies have shown that histamine secretion by mast cells, in response to either antigens or synthetic polycations, is mediated by a rapid, compound exocytosis (I, 3, 15, 16, 18, 19, 28). Early in the secretory process, single granules fuse with the plasma membrane, whereas at later stages membranes of adjacent granules in the cell interior fuse in succession to produce deep invaginations in the cell surface (1,19,28). These morphological observations correlate well with chemical measurements of release showing that 40-80% of the total cell histamine is secreted within 2 min (3, 28). There is good evidence that secretion is initiated by a rise in intracellular calcium activity (9,10,16,17,22), and for this reason the mast cell represents an important model of calcium-mediated stimulus-secretion coupling (8,12).This rapid exocytotic response of the mast cell has proven extremely useful for studying membrane fusion because numerous fusion events occur within a short period ; electron microscopy studies have already demonstrated what appear to be preliminary stages in this process. In thin sections of stimulated mast cells, granule membranes often contact the plasma membrane at sites where the intervening cytoplasm has been expressed (7,21), forming what Palade and Bruns (25) termed a "pentalaminar figure ." The occurrence of these structures in many types of secretory cells during exocytosis has suggested that they are a preliminary stage in membrane fusion (2,24,29,30) . In mast cells these contacts can be extensive and are often seen where the granule bulges against the plasma membrane. In freeze-fracture, these bulges frequently have plasma membrane domes that have been cleared of intramembrane particles (IMP) (7, 21). Furthermore, Lawson et al. (21) have shown in thin sections that a variety of ferritin-conjugated surface ligands will not bind to the plasma membrane where it contacts an underlying secretory...

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confidence: 71%

“…This suggests that the first contact between the plasma and granule membranes is small and focal . Previous thin section studies of glutaraldehyde-fixed mast cells have on occasion demonstrated such localized contacts (1,4,20,28) .…”

Section: Discussionmentioning

confidence: 99%

Arrest of membrane fusion events in mast cells by quick-freezing.

Chandler¹,

Heuser

1980

The Journal of Cell Biology

238

122

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“…Compound exocytosis seems to be the major mechanism of secretion in mast cells stimulated either with compound 48/80 (Rohlich et al, 1971), bee venom (Bloom and Haegermark, 1967), or with antigens in sensitized cells (Anderson et al, 1973). Also, compound exocytosis seems to occur in human platelets (Morgenstern et al, 1987) and neutrophils (Chandler et al, 1983;Chandler and Kazilek, 1986).…”

Section: Discussionmentioning

confidence: 99%

Compound versus multigranular exocytosis in peritoneal mast cells.

Toledo

Fernández

1990

The Journal of General Physiology

132

122

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We have used the whole-cell patch-pipette technique to measure the step increases in the cell membrane capacitance (equivalent to the membrane area) caused by the fusion of secretory granules in degranulating murine mast cells. We have observed that up to 30% of the total membrane expansion caused by degranulation results from large fusion events that cannot be explained by the fusion of single secretory granules. These large events are observed mainly in the initial phase of a degranulation. We have developed a simple mathematical model for a mast cell to test whether these large events are caused by a stimulus-induced, granule-to-granule fusion that occurs before their exocytosis (multigranular exocytosis). Our results suggest that the large fusion events are caused by the exocytosis of granule aggregates that existed before stimulation and that are located at the cell's periphery. We propose a novel mechanism by which granule aggregates can be formed at the periphery of the cell. This mechanism relies on the ability of a transiently fused granule ("flicker") to fuse with more internally located granules in a sequential manner. This pattern may result in the formation of larger peripheral granules that later on can fuse with the membrane. The formation of peripheral granule aggregates may potentiate a subsequent secretory response.

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“…This process was repeated, resulting in a series of inter connected cavities, and thus directly communicating with the extracellular space. Anderson et al (18) using TEM observed that sequential exocytosis of histamine-storing granules takes place when sensitized rat peritoneal mast cells are incubated with antigen. Tizard and Holmes (19) studied degranulation of rat peritoneal mast cells by SEM following chemical treatment and exposure to a specific antigen.…”

Section: Discussionmentioning

confidence: 99%

Electron Microscopic Studies on the Inhibition of Degranulation of Rat Mast Cells by a Novel Anti-Allergic Agent, PTPC

Ohashi

Watanabe

Nishigaki

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-When rat mast cells sensitized by IgE antibody were exposed to antigen, transmission elec tron microscopy revealed alteration of the granules, cavity formation by fusion of the perigranular mem brane and granule release by the fusion of the cavity membrane with the mast cell membrane. Scanning elec tron microscopy disclosed the extrusion of smooth and round bodies from pores formed on the cell surface. These changes were accompanied by the release of histamine. The inhibition of this degranulation by a novel anti-allergic agent, 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (PTPC), was evalu ated quantitatively as an inhibition of the granule alteration and cavity formation. At a concentration of 100 nM, PTPC inhibited the granule alteration and cavity formation as well as histamine release. In the same concentration, PTPC significantly increased the cyclic AMP content in the mast cells. These results sug gest that the inhibition of the morphological changes in mast cells by PTPC might be due to the increased cyclic AMP caused by the agent and plays an important role in the suppression of chemical mediators re lease.

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Sequential Exocytosis of Storage Granules during Antigen‐Induced Histamine Release from Sensitized Rat Mast Cells in vitro An electron microscopic study

Abstract: ANDERSON, P., S. A. SLORACH and B. UVNXS. Sequential exocytosis of storage granules during antigen-induced histamine release from sensitized rat mast cells in vitro. Acta physiol. scand. 1973. 88. 359-372.

Cited by 97 publications

References 16 publications

Arrest of membrane fusion events in mast cells by quick-freezing.

Arrest of membrane fusion events in mast cells by quick-freezing.

Compound versus multigranular exocytosis in peritoneal mast cells.

Electron Microscopic Studies on the Inhibition of Degranulation of Rat Mast Cells by a Novel Anti-Allergic Agent, PTPC

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