scholarly journals Cytoskeletal Transport, Reorganization, and Fusion Regulation in Mast Cell-Stimulus Secretion Coupling

2021 ◽  
Vol 9 ◽  
Author(s):  
Gaël Ménasché ◽  
Cyril Longé ◽  
Manuela Bratti ◽  
Ulrich Blank
Keyword(s):  
Mast Cell ◽  
Inflammatory Diseases ◽  
Secretory Granules ◽  
Transport Mechanisms ◽  
Tight Coupling ◽  
Regulatory Cytokine ◽  
Stimulus Secretion Coupling ◽  
Granule Secretion ◽  
Cytoskeletal Elements ◽  
Insight Into

Mast cells are well known for their role in allergies and many chronic inflammatory diseases. They release upon stimulation, e.g., via the IgE receptor, numerous bioactive compounds from cytoplasmic secretory granules. The regulation of granule secretion and its interaction with the cytoskeleton and transport mechanisms has only recently begun to be understood. These studies have provided new insight into the interaction between the secretory machinery and cytoskeletal elements in the regulation of the degranulation process. They suggest a tight coupling of these two systems, implying a series of specific signaling effectors and adaptor molecules. Here we review recent knowledge describing the signaling events regulating cytoskeletal reorganization and secretory granule transport machinery in conjunction with the membrane fusion machinery that occur during mast cell degranulation. The new insight into MC biology offers novel strategies to treat human allergic and inflammatory diseases targeting the late steps that affect harmful release from granular stores leaving regulatory cytokine secretion intact.

scholarly journals Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ofir Klein ◽  
Ronit Sagi-Eisenberg
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Cell Types ◽  
Secretory Cells ◽  
Regulated Exocytosis ◽  
Open Questions ◽  
Conflicting Evidence ◽  
Compound Exocytosis

Anaphylaxis is a notorious type 2 immune response which may result in a systemic response and lead to death. A precondition for the unfolding of the anaphylactic shock is the secretion of inflammatory mediators from mast cells in response to an allergen, mostly through activation of the cells via the IgE-dependent pathway. While mast cells are specialized secretory cells that can secrete through a variety of exocytic modes, the most predominant mode exerted by the mast cell during anaphylaxis is compound exocytosis—a specialized form of regulated exocytosis where secretory granules fuse to one another. Here, we review the modes of regulated exocytosis in the mast cell and focus on compound exocytosis. We review historical landmarks in the research of compound exocytosis in mast cells and the methods available for investigating compound exocytosis. We also review the molecular mechanisms reported to underlie compound exocytosis in mast cells and expand further with reviewing key findings from other cell types. Finally, we discuss the possible reasons for the mast cell to utilize compound exocytosis during anaphylaxis, the conflicting evidence in different mast cell models, and the open questions in the field which remain to be answered.

scholarly journals Pancreatic β-cells express hepcidin, an iron-uptake regulatory peptide

2008 ◽  
Vol 197 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Hasan Kulaksiz ◽  
Evelyn Fein ◽  
Peter Redecker ◽  
Wolfgang Stremmel ◽  
Guido Adler ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Secretory Granules ◽  
Rinm5f Cells ◽  
Β Cells ◽  
Additional Source ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Vital Functions ◽  
Immunohistochemical Studies ◽  
Insight Into

Body iron is involved in various vital functions. Its uptake in the intestine is regulated by hepcidin, a bioactive peptide originally identified in plasma and urine and subsequently in the liver. In the present study, we provide evidence at the transcriptional and translational levels that hepcidin is also expressed in the pancreas of rat and man. Immunohistochemical studies localized the peptide exclusively to β-cells of the islets of Langerhans. Immunoelectron microscopical analyses revealed that hepcidin is confined to the insulin-storing β-cell secretory granules. As demonstrated in insulinoma-derived RINm5F cells, the expression of hepcidin in β-cells is regulated by iron. Based on the present findings we conclude that pancreatic islets are an additional source of the peptide hepcidin. The localization of this peptide to β-cells suggests that pancreatic β-cells may be involved in iron metabolism in addition to their genuine function in blood glucose regulation. In view of the various linked iron/glucose disorders in the pancreas, the present findings may provide an insight into the phenomenology of intriguing mutual relationships between iron and glucose metabolisms.

scholarly journals Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qin Gong ◽  
Kim Robinson ◽  
Chenrui Xu ◽  
Phuong Thao Huynh ◽  
Kelvin Han Chung Chong ◽  
...  
Keyword(s):  
Cell Death ◽  
Inner Core ◽  
Inflammatory Diseases ◽  
Structural Features ◽  
Structural Basis ◽  
Cultured Human Cells ◽  
Structural Insight ◽  
Sensor Proteins ◽  
Insight Into

AbstractNod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIINDUPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells—a process that is greatly enhanced by NLRP1-FIINDUPA which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.

scholarly journals Mouse Mast Cell Secretory Granules Can Function as Intracellular Ionic Oscillators

2001 ◽  
Vol 80 (5) ◽  
pp. 2133-2139 ◽  
Author(s):  
Ivan Quesada ◽  
Wei-Chun Chin ◽  
Jordan Steed ◽  
Patricia Campos-Bedolla ◽  
Pedro Verdugo
Keyword(s):  
Mast Cell ◽  
Secretory Granules ◽  
Mouse Mast Cell

scholarly journals The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2491-2506 ◽  
Author(s):  
Gökhan Cildir ◽  
Harshita Pant ◽  
Angel F. Lopez ◽  
Vinay Tergaonkar
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Small Population ◽  
Transcriptional Program ◽  
Cell Functions ◽  
New Concepts ◽  
Health And Disease ◽  
Ige Mediated

Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.

An Insight into the Polymeric Nanoparticles Applications in Diabetes Diagnosis and Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Parisa Dehghani ◽  
Monireh Esameili Rad ◽  
Atefeh Zarepour ◽  
Ponnurengam Malliappan Sivakumar ◽  
Ali Zarrabi
Keyword(s):  
Polymeric Nanoparticles ◽  
Synthetic Polymers ◽  
Diagnostic Methods ◽  
Diagnosis And Treatment ◽  
Diabetes Diagnosis ◽  
Transport Mechanisms ◽  
Different Types ◽  
Treatment And Diagnosis ◽  
Insight Into

: Diabetes mellitus (DM) is a type of chronic metabolic disease that has affected millions of people worldwide and is known with a defect in the amount of insulin secretion, insulin functions, or both. This deficiency leads to an increase in the amounts of glucose, which could be accompanied by long-term damages to other organs such as eyes, kidneys, heart, and nervous system. Thus, introducing an appropriate approach for diagnosis and treatment of different types of DM is the aim of several researches. By the emergence of nanotechnology and its application in medicine, new approaches were presented for these purposes. The object of this review article is to introduce different types of polymeric nanoparticles (PNPs), as one of the most important classes of nanoparticles, for diabetic management. To achieve this goal, at first, some of the conventional therapeutic and diagnostic methods of DM will be reviewed. Then, different types of PNPs, in two forms of natural and synthetic polymers with different properties, as a new method for DM treatment and diagnosis will be introduced. In the next section, the transport mechanisms of these types of nano-carriers across the epithelium, via paracellular and transcellular pathways will be explained. Finally, the clinical use of PNPs in the treatment and diagnosis of DM will be summarized. Based on the results of this literature review, PNPs could be considered one of the most promising methods for DM management.

The lysosomal protease cathepsin D is efficiently sorted to and secreted from regulated secretory compartments in the rat basophilic/mast cell line RBL

2000 ◽  
Vol 113 (18) ◽  
pp. 3289-3298 ◽  
Author(s):  
A. Dragonetti ◽  
M. Baldassarre ◽  
R. Castino ◽  
M. Demoz ◽  
A. Luini ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Line ◽  
Cathepsin D ◽  
Secretory Granules ◽  
Bioactive Molecules ◽  
Blue Staining ◽  
Lysosomal Protease ◽  
Mannose 6 Phosphate ◽  
Mast Cell Line

Basophils and mast cells contain a peculiar class of inflammatory granules that discharge their content upon antigen-mediated crosslinking of IgE-membrane receptors. The pathways for granule biogenesis and exocytosis in these cells are still largely obscure. In this study we employed the rat basophilic leukemia (RBL)/mast cell line to verify the hypothesis that inflammatory granules share common bioactive molecules and functional properties with lysosomes. We demonstrate that inflammatory granules, as identified by the monoclonal 5G10 antibody (which recognises an integral membrane protein) or by Toluidine Blue staining, have an intralumenal acidic pH, possess lysosomal enzymes and are accessible by fluid-phase and membrane endocytosis markers. In addition, we studied the targeting, subcellular localisation and regulated secretion of the lysosomal aspartic protease cathepsin D (CD) as affected by IgE receptor stimulation in order to obtain information on the pathways for granule biogenesis and exocytosis. Stimulation with DNP-BSA of specific IgE-primed RBL cells led to a prompt release of processed forms of CD, along with other mature lysosomal hydrolases. This release could be prevented by addition of EGTA, indicating that it was dependent on extracellular calcium influx. Antigen stimulation also induced exocytosis of immature CD forms accumulated by ammonium chloride, suggesting the existence of an intermediate station in the pathway for granule biogenesis still sensitive to regulated exocytosis. The targeting of molecules to secretory granules may occur via either a mannose-6-phosphate-dependent or mannose-6-phosphate-independent pathway. We conclude that endosomes and lysosomes in basophils/mast cells can act as regulated secretory granules or actually identify with them.

scholarly journals The Search for Supernova-Produced Radionuclides in Terrestrial Deep-Sea Archives

2012 ◽  
Vol 29 (2) ◽  
pp. 109-114 ◽  
Author(s):  
J. Feige ◽  
A. Wallner ◽  
S. R. Winkler ◽  
S. Merchel ◽  
L. K. Fifield ◽  
...  
Keyword(s):  
Solar System ◽  
Marine Sediment ◽  
Deep Sea ◽  
Massive Stars ◽  
Sediment Cores ◽  
Deep Ocean ◽  
Transport Mechanisms ◽  
Supernova Shell ◽  
Process Element ◽  
Insight Into

AbstractAn enhanced concentration of 60Fe was found in a deep ocean crust in 2004 in a layer corresponding to an age of ∼2 Myr. The confirmation of this signal in terrestrial archives as supernova-induced and the detection of other supernova-produced radionuclides is of great interest. We have identified two suitable marine sediment cores from the South Australian Basin and estimated the intensity of a possible signal of the supernova-produced radionuclides 26Al, 53Mn, 60Fe, and the pure r-process element 244Pu in these cores. The finding of these radionuclides in a sediment core might allow us to improve the time resolution of the signal and thus to link the signal to a supernova event in the solar vicinity ∼2 Myr ago. Furthermore, it gives us an insight into nucleosynthesis scenarios in massive stars, condensation into dust grains and transport mechanisms from the supernova shell into the solar system.

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