Limits...
The SNARE Machinery in Mast Cell Secretion.

Lorentz A, Baumann A, Vitte J, Blank U - Front Immunol (2012)

Bottom Line: During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines.Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis.In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Medicine, University of Hohenheim Stuttgart, Germany.

ABSTRACT
Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

No MeSH data available.


Related in: MedlinePlus

Possible cytokine secretion pathways in mast cells. Cytokine secretion may occur constitutively through small vesicular carriers or through recycling endosomes (ER) as described for TNF in macrophages. Moreover, TNF could get re-endocytosed from the plasma membrane and transported into secretory granules (SG) and then rapidly released upon stimulation. Another possible pathway of regulated exocytosis in mast cells may be piecemeal degranulation as reported for eosinophils.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3367400&req=5

Figure 3: Possible cytokine secretion pathways in mast cells. Cytokine secretion may occur constitutively through small vesicular carriers or through recycling endosomes (ER) as described for TNF in macrophages. Moreover, TNF could get re-endocytosed from the plasma membrane and transported into secretory granules (SG) and then rapidly released upon stimulation. Another possible pathway of regulated exocytosis in mast cells may be piecemeal degranulation as reported for eosinophils.

Mentions: VAMP8 was the first SNARE protein examined for a role in cytokine/chemokine trafficking in mast cells. As already mentioned above, we and others found in BMMC that absence of VAMP8 did not affect secretion of several chemokines or cytokines tested contrasting with some recent data showing an implication of VAMP8 in anaphylatoxin-induced TNF release in macrophages (Tiwari et al., 2008; Pushparaj et al., 2009). For the latter its implication in cytokine release was specific for TNF as IL-1β, IL-6, and CCL3 were not affected. In wild-type macrophages, TNF was found to colocalize with VAMP8-positive vesicles, and in VAMP8-deficient macrophages, TNF release was inhibited (Tiwari et al., 2008; Pushparaj et al., 2009). Furthermore, VAMP8 has been shown to regulate the release of TNF and β-hexosaminidase in macrophages triggered by fMLP (Alvarez de Toledo and Fernandez, 1990). In mast cells, TNF did not colocalize with VAMP8-containing vesicles, but was rather found to colocalize with a VAMP3 positive compartment in a manner similar to the compartments described for release of TNF into the phagocytotic cup (Tiwari et al., 2008). Given that VAMP3 has been associated with the recycling endosomal compartment this opens the possibility of trafficking through such a compartment prior to release. Interestingly, further studies in human mast cell lines showed that TNF traffics to the membrane, from where it gets re-endocytosed into cytoplasmic granules suggesting that granular localization could depend on a specific mechanism of re-endocytosis (Olszewski et al., 2007) although direct sorting via a Mannose phosphate receptor-dependent pathway has also been proposed in rodent mast cells (Olszewski et al., 2006). On the other hand, when analyzing BMMC, we did not see significant granule localization by probing with an antibody detecting endogenously produced TNF and rather found TNF co-localized with VAMP3-containing fractions. Yet, in some isolated cells we were also able to detect TNF in SG. This agrees with previous data showing that in BMMC a small, but detectable fraction (<10%) of TNF gets mobilized rapidly being in line with a SG storage mode (Gordon and Galli, 1991). Figure 3 summarizes possible cytokine secretion pathways in mast cells.


The SNARE Machinery in Mast Cell Secretion.

Lorentz A, Baumann A, Vitte J, Blank U - Front Immunol (2012)

Possible cytokine secretion pathways in mast cells. Cytokine secretion may occur constitutively through small vesicular carriers or through recycling endosomes (ER) as described for TNF in macrophages. Moreover, TNF could get re-endocytosed from the plasma membrane and transported into secretory granules (SG) and then rapidly released upon stimulation. Another possible pathway of regulated exocytosis in mast cells may be piecemeal degranulation as reported for eosinophils.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367400&req=5

Figure 3: Possible cytokine secretion pathways in mast cells. Cytokine secretion may occur constitutively through small vesicular carriers or through recycling endosomes (ER) as described for TNF in macrophages. Moreover, TNF could get re-endocytosed from the plasma membrane and transported into secretory granules (SG) and then rapidly released upon stimulation. Another possible pathway of regulated exocytosis in mast cells may be piecemeal degranulation as reported for eosinophils.
Mentions: VAMP8 was the first SNARE protein examined for a role in cytokine/chemokine trafficking in mast cells. As already mentioned above, we and others found in BMMC that absence of VAMP8 did not affect secretion of several chemokines or cytokines tested contrasting with some recent data showing an implication of VAMP8 in anaphylatoxin-induced TNF release in macrophages (Tiwari et al., 2008; Pushparaj et al., 2009). For the latter its implication in cytokine release was specific for TNF as IL-1β, IL-6, and CCL3 were not affected. In wild-type macrophages, TNF was found to colocalize with VAMP8-positive vesicles, and in VAMP8-deficient macrophages, TNF release was inhibited (Tiwari et al., 2008; Pushparaj et al., 2009). Furthermore, VAMP8 has been shown to regulate the release of TNF and β-hexosaminidase in macrophages triggered by fMLP (Alvarez de Toledo and Fernandez, 1990). In mast cells, TNF did not colocalize with VAMP8-containing vesicles, but was rather found to colocalize with a VAMP3 positive compartment in a manner similar to the compartments described for release of TNF into the phagocytotic cup (Tiwari et al., 2008). Given that VAMP3 has been associated with the recycling endosomal compartment this opens the possibility of trafficking through such a compartment prior to release. Interestingly, further studies in human mast cell lines showed that TNF traffics to the membrane, from where it gets re-endocytosed into cytoplasmic granules suggesting that granular localization could depend on a specific mechanism of re-endocytosis (Olszewski et al., 2007) although direct sorting via a Mannose phosphate receptor-dependent pathway has also been proposed in rodent mast cells (Olszewski et al., 2006). On the other hand, when analyzing BMMC, we did not see significant granule localization by probing with an antibody detecting endogenously produced TNF and rather found TNF co-localized with VAMP3-containing fractions. Yet, in some isolated cells we were also able to detect TNF in SG. This agrees with previous data showing that in BMMC a small, but detectable fraction (<10%) of TNF gets mobilized rapidly being in line with a SG storage mode (Gordon and Galli, 1991). Figure 3 summarizes possible cytokine secretion pathways in mast cells.

Bottom Line: During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines.Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis.In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Medicine, University of Hohenheim Stuttgart, Germany.

ABSTRACT
Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

No MeSH data available.


Related in: MedlinePlus