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Journal of Fungi (Basel, Switzerland) Jun 2021Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share... (Review)
Review
Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share the ability to store antimicrobial compounds in membrane bound organelles that can be immediately deployed to eradicate or inhibit growth of invading pathogens. These membrane-bound organelles consist of secretory vesicles or granules, which move to the surface of the cell, where they fuse with the plasma membrane to release their contents in the process of degranulation. Lymphocytes, macrophages, neutrophils, mast cells, eosinophils, and basophils all degranulate in fungal host defence. While anti-microbial secretory vesicles are shared among different immune cell types, information about each cell type has emerged independently leading to an uncoordinated and confusing classification of granules and incomplete description of the mechanism by which they are deployed. While there are important differences, there are many similarities in granule morphology, granule content, stimulus for degranulation, granule trafficking, and release of granules against fungal pathogens. In this review, we describe the similarities and differences in an attempt to translate knowledge from one immune cell to another that may facilitate further studies in the context of fungal host defence.
PubMed: 34208679
DOI: 10.3390/jof7060484 -
Biomedicine & Pharmacotherapy =... Jul 2020Mast cells (MCs) degranulation is a key process during the allergic inflammatory response. MCs release their preformed and new synthesized granules after activation. We...
Mast cells (MCs) degranulation is a key process during the allergic inflammatory response. MCs release their preformed and new synthesized granules after activation. We found that granules were released partially and selectively after the activation of bone marrow-derived mouse mast cells (BMMCs). Next, we investigated the response of degranulated MCs to a new challenge. BMMCs were activated by antibody/antigen (IgE/Ag) or compound 48/80 (C48/80). The degranulated BMMCs were then reactivated by either IgE/Ag or C48/80 without time intervals. Flow cytometry was used to detect the expression of CD117, FcεRI, and intracellular granules of BMMCs, and BMMCs degranulation was detected using the β-hexosaminidase release assay. The morphology of BMMCs was observed by staining with toluidine blue. Degranulated BMMCs activated by IgE/Ag failed to respond to the same IgE/Ag challenge and released β-hexosaminidase independent of unoccupied FcεRI, but responded to C48/80. Degranulated BMMCs activated by C48/80 responded to either IgE/Ag or C48/80. These results indicated that degranulated BMMCs could be reactivated and released granule mediators again, this revealed the unique mediator releasing mechanism of degranulated MCs and their potential function in maintaining inflammation or causing hypersensitivity.
Topics: Animals; Antigens; Bone Marrow Cells; Cell Degranulation; Cells, Cultured; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred BALB C; p-Methoxy-N-methylphenethylamine
PubMed: 32388238
DOI: 10.1016/j.biopha.2020.110157 -
Translational Pediatrics Mar 2024Eosinophilic esophagitis is a chronic inflammatory disorder, often relapsing. There is an increasing need to develop new alternative diagnostic and monitoring methods on... (Review)
Review
Eosinophilic esophagitis: absolute eosinophilic count, peak eosinophilic count, and potential biomarkers of eosinophilic degranulation products-an in-depth systematic review.
BACKGROUND
Eosinophilic esophagitis is a chronic inflammatory disorder, often relapsing. There is an increasing need to develop new alternative diagnostic and monitoring methods on a critical basis, which will provide samples through none or minimally invasive procedures. This study aims to identify and document the types and roles of potential biomarkers in eosinophilic esophagitis released by eosinophils as well as the potential relationship to the peak eosinophilic count and the degree of degranulation of eosinophils (DGE/DGE + NDGE: degranulated eosinophils/degranulated eosinophils and non-degranulated eosinophils).
METHODS
This is the first in-depth systematic review study using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) parameters involving a literature search of academic databases (PubMed, Scopus, Medline, Google Scholar, and Cochrane Database, 2011-2022) targeting specifically the eosinophilic counts and ratio, and the eosinophilic degranulation products as potential biomarkers. Data were extracted from ten selected studies and presented on a spreadsheet.
RESULTS
The studies show the ability to detect eosinophilic and non-eosinophilic degranulation products, and absolute eosinophilic count in samples, including blood and urine, thereby serving as potential surrogates in making the diagnosis or monitoring disease progression in the future. There is an obvious paucity of studies that correlate potential biomarkers to the degree of degranulation of eosinophils.
CONCLUSIONS
A few minimally invasive methods and biomarkers may be suggested as alternative tools in diagnosing and monitoring eosinophilic esophagitis. While there is no consensus on the clinical usefulness of these biomarkers, our critical evaluation may suggest that the eosinophilic degranulation ratio (DGE/DGE + NDGE: degranulated eosinophils/degranulated eosinophils and non-degranulated eosinophils) in the esophagus may be critical for evaluating properly these biomarkers. An increasing trend may culminate in the potential clinical use of these biomarkers evaluated not only with the peak eosinophilic count, but also with the degranulation score upon regulatory bodies' approval to monitor eosinophilic esophagitis in the future. We strongly advocate for the necessity to score the esophageal biopsies with both a peak eosinophilic count and a score of the degranulated eosinophils.
PubMed: 38590372
DOI: 10.21037/tp-23-478 -
The American Journal of Pathology Aug 1972Platelet degranulation is a characteristic feature of platelet response to aggregating agents, but the mechanism and route by which secretory organelles are transferred...
Platelet degranulation is a characteristic feature of platelet response to aggregating agents, but the mechanism and route by which secretory organelles are transferred to plasma are still uncertain. In the present study, human platelets were incubated with cytochalasin B, an agent which stabilizes discoid shape, and trypsin, which is known to cause release reaction and degranulation. Platelets treated in this manner retained their disc form, but were nearly devoid of granules and dense bodies. Electron-dense tracers indicated that degranulation was accomplished by fusion of secretory organelles with channels of the open canalicular system. The degranulated discoid platelet appears to survive exposure to cytochalasin B and trypsin and may prove to be a useful model for in vivo and in vitro experimental studies.
Topics: Biological Products; Blood Platelets; Cytoplasm; Cytoplasmic Granules; Humans; Indoles; Microtubules; Mitochondria; Peroxidases; Plants; Platelet Adhesiveness; Thorium Dioxide; Trypsin
PubMed: 5049426
DOI: No ID Found -
Journal of Periodontology Feb 2013Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast... (Comparative Study)
Comparative Study
BACKGROUND
Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in periodontal diseases, and the effects of mast cell degranulation on the chronic stages of non-allergic inflammation, particularly in periodontitis, are not known. The present study analyzes the relationship between the mast cell degranulation and human periodontal disease progression.
METHODS
A total of 50 clinical specimens including moderate periodontitis (n = 17), advanced periodontitis (n = 18), and healthy control tissues (n = 15) were used in this study. All specimens were fixed in 10% buffered formalin and stained with hematoxylin and eosin for histopathology, with toluidine blue for identifying mast cells, and by immunohistochemistry for the expressions of mast cell tryptase in periodontal tissues. The total and degranulated mast cell densities (per high-power field) were quantified in the specimens.
RESULTS
Compared with healthy controls, there were significantly increased both total and degranulated mast cell densities in human moderate (P <0.01) and advanced (P <0.01) periodontitis groups by toluidine blue staining, and there were significantly higher densities of both total and degranulated tryptase-positive mast cell subpopulation in the moderate periodontitis group (P <0.01) and even significantly higher subpopulation densities in the advanced periodontitis group by immunohistochemical staining, in which both total and degranulated mast cell densities were significantly higher in the advanced periodontitis group than those in the moderate periodontitis group (P <0.01) by both toluidine blue staining and immunohistochemical staining. There was significantly more severe periodontal inflammatory pathology in the advanced periodontitis group than in the moderate periodontitis group (P <0.01).
CONCLUSION
These findings indicate a significant correlation among tryptase-positive mast cell density, the degree of their degranulation, and the human periodontitis severity, and the results of this study further indicate that mast cell degranulation appears to be associated with human periodontal disease.
Topics: Adult; Alveolar Bone Loss; Cell Count; Cell Degranulation; Coloring Agents; Disease Progression; Female; Humans; Immunohistochemistry; Lymphocytes; Macrophages; Male; Mast Cells; Middle Aged; Neutrophils; Periodontal Attachment Loss; Periodontitis; Periodontium; Plasma Cells; Tolonium Chloride; Tooth Mobility; Tryptases; Young Adult
PubMed: 22509749
DOI: 10.1902/jop.2012.120066 -
The Journal of Experimental Medicine Dec 1960A marked reduction in numbers of cytoplasmic granules in rabbit and human polymorphonuclear leucocytes takes place following ingestion of various microorganisms or of a...
A marked reduction in numbers of cytoplasmic granules in rabbit and human polymorphonuclear leucocytes takes place following ingestion of various microorganisms or of a yeast cell wall preparation. The degranulation occurs within 30 minutes of phagocytosis, and is directly related to the quantity of material engulfed. White cells completely degranulated following phagocytosis of large numbers of microorganisms remain viable for at least 1 hour. The granules of polymorphonuclear leucocytes contain the antimicrobial agent, phagocytin, and various digestive enzymes. These substances thus are released into the cytoplasm or into vacuoles following ingestion of foreign material. The granule system and granule lysis mechanism may well play a central role in the primary function of these specialized cells; namely, that of destroying invading microorganisms.
Topics: Animals; Cytoplasm; Cytoplasmic Granules; Humans; Leukocytes; Neutrophils; Phagocytosis; Rabbits; Vacuoles
PubMed: 13714579
DOI: 10.1084/jem.112.6.1005 -
Biochimica Et Biophysica Acta. General... Nov 2017Mast cells are important modulators of the human immune system via their release of several inflammatory mediators and proteases. The release can be activated by...
BACKGROUND
Mast cells are important modulators of the human immune system via their release of several inflammatory mediators and proteases. The release can be activated by different pathways: the classical immunoglobulin E-dependent pathway and by the non-immunological immunoglobulin E-independent pathway. MAS-related G protein-coupled receptor X2 (MRGPRX2) is expressed in mast cells and it is one of the endogenous receptor responsible for the IgE-independent activation of human mast cell. The MRGPRX2 is classified as orphan receptor and unlike most GPCRs, the MRGPRX2 recognizes a wide range of basic molecules. Thus, there still might be several unknown ligands for the receptor.
METHODS
MRGPRX2 activating peptides were isolated from human plasma using consecutive HPLC purification steps. The isolation process was monitored with MRGPRX2 transfected HEK 293 cells. The isolated peptides were sequenced by MS and synthetized. The synthetic peptides were used to determine degranulation of the human LAD 2 mast cell line by measuring β-hexosaminidase release.
RESULTS
Three endogenous MRGPRX2 activating peptides were isolated from human plasma. These peptides are identified as fragments of albumin. The isolated fragments activate MRGPRX2 and degranulate MRGPRX2 expressing LAD 2 cells in dose-dependent manner.
CONCLUSIONS
The isolated basic peptides generated from human albumin are able to degranulate mast cells via the MRGPRX2.
GENERAL SIGNIFICANCE
These endogenous albumin fragments, cleaved from albumin by mast cell secreted proteases, provide a possible pathway for self-perpetuating mast cell dependent inflammation.
Topics: Cell Degranulation; HEK293 Cells; Humans; Immunoglobulin E; Ligands; Mast Cells; Nerve Tissue Proteins; Peptide Library; Peptides; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Serum Albumin, Human; Signal Transduction; beta-N-Acetylhexosaminidases
PubMed: 28844982
DOI: 10.1016/j.bbagen.2017.08.013 -
The Korean Journal of Parasitology Mar 2005Eosinophil degranulation is considered to be a key effector function for the killing of helminthic worms and tissue inflammation at worm-infected lesion sites. However,...
Eosinophil degranulation is considered to be a key effector function for the killing of helminthic worms and tissue inflammation at worm-infected lesion sites. However, relatively little data are available with regard to eosinophil response after stimulation with worm-secreted products which contain a large quantity of cysteine proteases. In this study, we attempted to determine whether the degranulation of human eosinophils could be induced by the direct stimulation of the excretory-secretory products (ESP) of Paragonimus westermani, which causes pulmonary paragonimiasis in human beings. Incubation of eosinophils for 3 hr with Paragonimus-secreted products resulted in marked degranulation, as evidenced by the release of eosinophil-derived neurotoxin (EDN) in the culture supernatants. Moreover, superoxide anion was produced by eosinophils after stimulation of the ESP. The ESP-induced EDN release was found to be significantly inhibited when the ESP was pretreated with protease inhibitor cocktail or the cysteine protease inhibitor, E-64. These findings suggest that human eosinophils become degranulated in response to P. westermani-secreted proteases, which may contribute to in vivo tissue inflammation around the worms.
Topics: Animals; Cell Degranulation; Cysteine Endopeptidases; Eosinophil-Derived Neurotoxin; Eosinophils; Humans; Paragonimus westermani; Superoxides; Time Factors
PubMed: 15793357
DOI: 10.3347/kjp.2005.43.1.33 -
Acta Anatomica 1992In the preferential harvesting of rounded mitotic (M phase) cells of human Chang liver monolayer cultures by mechanical agitation in Ca(2+)-free phosphate-buffered...
In the preferential harvesting of rounded mitotic (M phase) cells of human Chang liver monolayer cultures by mechanical agitation in Ca(2+)-free phosphate-buffered saline, degranulation of endoplasmic reticulum (ER) was observed. Mitotic cells are known to have a series of Ca2+ transients and, without being subjected to Ca(2+)-free washings, did not have degranulated ER. Quiescent cells incubated with 0.7 mM adenosine 5'-triphosphate (ATP) in Ca(2+)-free HEPES-buffered saline produced very similar ER degranulations. Confocal argon laser imaging of fluo-3-loaded cells showed a Ca2+ transient peaking at 2 min after ATP treatment. In the absence of extracellular Ca2+, transients of Ca2+ elevation in the cytosol would exit the cell in a down-gradient, draining the ER Ca2+ stores. Substituting ATP with 1 microM brominated A23187 calcium ionophore in the incubation that contained 1-100 mM CaCl2, respectively, did not produce ER degranulation, thereby excluding raised cytosolic Ca2+ per se as the cause of ER degranulation. In fact, incubation with 0.7 mM ATP in the presence of 1-5 mM CaCl2 failed to produce ER degranulation. ER degranulated cells, from treatment with ATP without extracellular Ca2+ as well as from Ca(2+)-free washings at M phase, could be rescued by subsequent incubation in growth medium that contains Ca2+ whereupon the rounded cells re-flatten (a round-to-flat change) and have well-defined rough ER. It therefore seems possible for Ca2+ depletion, or at least a reduction, to be causally related to ER degranulation. If that were the case, ER granularity would appear to be a facultative rather than a constitutive state.
Topics: Adenosine Triphosphate; Calcium; Cell Degranulation; Cells, Cultured; Endoplasmic Reticulum; Humans; Interphase; Liver; Microscopy, Electron; Mitosis
PubMed: 1441882
DOI: 10.1159/000147352 -
British Journal of Haematology Jan 1985Myeloperoxidase (MPO)-deficient neutrophils (PMN) released considerably more beta-glucuronidase, lysozyme and vitamin B12-binding activities, when exposed to opsonized...
Myeloperoxidase (MPO)-deficient neutrophils (PMN) released considerably more beta-glucuronidase, lysozyme and vitamin B12-binding activities, when exposed to opsonized zymosan (STZ), than the normal counterpart. Release of the soluble enzyme lactate dehydrogenase was not appreciably changed over the incubation time with particles in either cell type. MPO-deficient PMN and normal PMN ingested STZ particles at a similar rate at early times, but thereafter phagocytosis by MPO-deficient PMN was significantly higher than that by normal PMN. The difference in degranulation between the two cell types greatly exceeded the difference in ingestion and was evident already at early phagocytosis times when no difference in phagocytosis was observed; this suggested that the higher degranulation in MPO-deficient PMN was at least in part independent of the increased ingestion. This was confirmed by experiments with the soluble stimulant N-formyl-L-norleucyl-L-leucyl-phenylalanine (FNLLP). MPO-deficient PMN and normal PMN exhibited a comparable respiratory burst when exposed to FNLLP plus cytochalasin B, but the defective cells released more azurophilic and specific granule markers than normal PMN. These results indicate that MPO-deficient PMN degranulate more than normal PMN and suggest a role for MPO in the regulation of degranulation.
Topics: Cytoplasmic Granules; Glucuronidase; Granulocytes; Humans; Muramidase; Neutrophils; Oligopeptides; Peroxidase; Peroxidases; Phagocytosis; Vitamin B 12; Zymosan
PubMed: 2982389
DOI: 10.1111/j.1365-2141.1985.tb02971.x