scholarly journals Distorted Secretory Granule Composition in Mast Cells with Multiple Protease Deficiency

2013 ◽  
Vol 191 (7) ◽  
pp. 3931-3938 ◽  
Author(s):  
Mirjana Grujic ◽  
Gabriela Calounova ◽  
Inger Eriksson ◽  
Thorsten Feyerabend ◽  
Hans-Reimer Rodewald ◽  
...  
Keyword(s):  
2009 ◽  
Vol 46 (3) ◽  
pp. 422-428 ◽  
Author(s):  
Tiago Braga ◽  
Maria Ringvall ◽  
Heidi Tveit ◽  
Magnus Åbrink ◽  
Gunnar Pejler

2011 ◽  
Vol 128 (6) ◽  
pp. 1310-1317.e8 ◽  
Author(s):  
Bo Wang ◽  
Juan Jia ◽  
Xiao Zhang ◽  
Eyal Zcharia ◽  
Israel Vlodavsky ◽  
...  
Keyword(s):  

1973 ◽  
Vol 51 (12) ◽  
pp. 1001-1004 ◽  
Author(s):  
T. Kanno ◽  
D. E. Cochrane ◽  
W. W. Douglas

Injection of Ca (but not Mg or K) through micropipettes placed within rat peritoneal mast cells elicited extrusion of secretory granules. The result is considered direct support for the view that a rise in the intracellular concentration of Ca ions suffices to induce exocytosis and accounts for the general requirement for Ca in stimulus–secretion coupling.


2018 ◽  
Vol 293 (21) ◽  
pp. 8217-8229 ◽  
Author(s):  
Stephen Bruinsma ◽  
Declan J. James ◽  
Melanie Quintana Serrano ◽  
Joseph Esquibel ◽  
Sang Su Woo ◽  
...  

Ca2+-dependent secretory granule fusion with the plasma membrane is the final step for the exocytic release of inflammatory mediators, neuropeptides, and peptide hormones. Secretory cells use a similar protein machinery at late steps in the regulated secretory pathway, employing protein isoforms from the Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families. However, no small-molecule inhibitors of secretory granule exocytosis that target these proteins are currently available but could have clinical utility. Here we utilized a high-throughput screen of a 25,000-compound library that identified 129 small-molecule inhibitors of Ca2+-triggered secretory granule exocytosis in RBL-2H3 mast cells. These inhibitors broadly fell into six different chemical classes, and follow-up permeable cell and liposome fusion assays identified the target for one class of these inhibitors. A family of 2-aminobenzothiazoles (termed benzothiazole exocytosis inhibitors or bexins) was found to inhibit mast cell secretory granule fusion by acting on a Ca2+-dependent, C2 domain–containing priming factor, Munc13-4. Our findings further indicated that bexins interfere with Munc13-4–membrane interactions and thereby inhibit Munc13-4–dependent membrane fusion. We conclude that bexins represent a class of specific secretory pathway inhibitors with potential as therapeutic agents.


1992 ◽  
Vol 175 (4) ◽  
pp. 1003-1012 ◽  
Author(s):  
M F Gurish ◽  
N Ghildyal ◽  
H P McNeil ◽  
K F Austen ◽  
S Gillis ◽  
...  

It is now established that the subclasses of mast cells (MC) that reside in mucosal and serosal environments can be distinguished from one another in terms of their expression of specific secretory granule-localized proteases and proteoglycans. Further, the hematopoietic- and connective tissue-derived cytokines that regulate expression of the genes that encode these constituents of the granule can now be identified using recently developed gene-specific probes and recombinant cytokines. When bone marrow-derived MC (BMMC) were developed with recombinant interleukin 3 (rIL-3) and maintained with this cytokine in the absence or presence of recombinant c-kit ligand (rKL), they remained safranin-, produced almost no 35S-labeled heparin proteoglycans, and contained greater levels of mouse MC protease (MMCP) -5 mRNA and mast cell carboxypeptidase A (MC-CPA) mRNA than MMCP-6 mRNA. They did not contain MMCP-4 or -2 mRNA, genes expressed late in the differentiation of progenitor cells into serosal and mucosal MCs, respectively. In contrast, BMMC developed with rKL alone or by sequential culture in medium containing rIL-3 followed by rKL expressed high levels of MMCP-4 and -6 mRNA, as well as the transcripts that encode MMCP-5 and MC-CPA. Although rKL-developed BMMC were safranin+ and produced substantial amounts of 35S-labeled heparin proteoglycans, they contained only minimal amounts of histamine and MC-CPA enzymatic activity relative to serosal MC. These are the first studies to characterize the transcriptional granule phenotype of a population of BMMC derived using any recombinant cytokine, to demonstrate a dissociation between histochemical staining and granule maturation, and to demonstrate antagonistic regulation of late expressed protease genes by a cytokine.


1980 ◽  
Vol 28 (12) ◽  
pp. 1351-1354 ◽  
Author(s):  
M R Robinovitch ◽  
D Lagunoff ◽  
J M Iversen

Rat parotid secretory granule preparations contain, in addition to the acinar secretory granules, a second type of granule. Whereas the acinar granules lyse under hypotonic conditions, this second type of granule does not, thus providing a means for obtaining a fraction sufficiently enriched in these granules to allow for their characterization. In the present study, these granules are shown to possess demonstrable chymotrypsin-like enzyme activity. In the intact rat parotid, such activity is shown by histochemical methods to be present in the numerous mast cells residing in the connective tissue stroma, but no such activity exists in any of the parenchymal cells. On the basis of their electron microscopic appearance, enzyme activity, and physical characteristics it is concluded that the second type of granule present in rat parotid secretory granule preparations originates from stromal mast cells rather than from parenchymal cells.


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