scholarly journals Increased Neutrophil Secretion Induced by NLRP3 Mutation Links the Inflammasome to Azurophilic Granule Exocytosis

2017 ◽  
Vol 7 ◽  
Author(s):  
Jennifer L. Johnson ◽  
Mahalakshmi Ramadass ◽  
Ariela Haimovich ◽  
Matthew D. McGeough ◽  
Jinzhong Zhang ◽  
...  
Keyword(s):  
Granule Exocytosis ◽  
Azurophilic Granule

scholarly journals Neutrophil azurophilic granule exocytosis is primed by TNF-α and partially regulated by NADPH oxidase

2016 ◽  
Vol 22 (8) ◽  
pp. 635-646 ◽  
Author(s):  
Renee M Potera ◽  
Melissa J Jensen ◽  
Brieanna M Hilkin ◽  
Gina K South ◽  
Jessica S Hook ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Tissue Damage ◽  
Chronic Inflammatory Disease ◽  
Host Tissue ◽  
Ros Generation ◽  
Oxygen Species ◽  
Granule Exocytosis ◽  
Azurophilic Granule ◽  
Tnf Α

Neutrophil (polymorphonuclear leukocyte) activation with release of granule contents plays an important role in the pathogenesis of acute lung injury, prompting clinical trials of inhibitors of neutrophil elastase. Despite mounting evidence for neutrophil-mediated host tissue damage in a variety of disease processes, mechanisms regulating azurophilic granule exocytosis at the plasma membrane, and thus release of elastase and other proteases, are poorly characterized. We hypothesized that azurophilic granule exocytosis would be enhanced under priming conditions similar to those seen during acute inflammatory events and during chronic inflammatory disease, and selected the cytokine TNF-α to model this in vitro. Neutrophils stimulated with TNF-α alone elicited intracellular reactive oxygen species (ROS) generation and mobilization of secretory vesicles, specific, and gelatinase granules. p38 and ERK1/2 MAPK were involved in these components of priming. TNF-α priming alone did not mobilize azurophilic granules to the cell surface, but did markedly increase elastase release into the extracellular space in response to secondary stimulation with N-formyl-Met-Leu-Phe (fMLF). Priming of fMLF-stimulated elastase release was further augmented in the absence of NADPH oxidase-derived ROS. Our findings provide a mechanism for host tissue damage during neutrophil-mediated inflammation and suggest a novel anti-inflammatory role for the NADPH oxidase.

scholarly journals Rab27a and Rab27b Regulate Neutrophil Azurophilic Granule Exocytosis and NADPH oxidase Activity by Independent Mechanisms

Traffic ◽  
2010 ◽  
Vol 11 (4) ◽  
pp. 533-547 ◽  
Author(s):  
Jennifer L. Johnson ◽  
Agnieszka A. Brzezinska ◽  
Tanya Tolmachova ◽  
Daniela B. Munafo ◽  
Beverly A. Ellis ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Granule Exocytosis ◽  
Nadph Oxidase Activity ◽  
Azurophilic Granule

scholarly journals Compensatory endocytosis occurs after cortical granule exocytosis in mouse eggs

2019 ◽  
Vol 235 (5) ◽  
pp. 4351-4360
Author(s):  
Matías D. Gómez‐Elías ◽  
Rafael A. Fissore ◽  
Patricia S. Cuasnicú ◽  
Débora J. Cohen
Keyword(s):  
Cortical Granule ◽  
Granule Exocytosis ◽  
Cortical Granule Exocytosis ◽  
Mouse Eggs

scholarly journals Calcineurin-dependent lytic granule exocytosis in NK-92 natural killer cells

2009 ◽  
Vol 254 (2) ◽  
pp. 105-109 ◽  
Author(s):  
Arun T. Pores-Fernando ◽  
Surabhi Gaur ◽  
Michelle Y. Doyon ◽  
Adam Zweifach
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Killer Cells ◽  
Granule Exocytosis ◽  
Lytic Granule

scholarly journals Counterregulation of clathrin-mediated endocytosis by the actin and microtubular cytoskeleton in human neutrophils

2009 ◽  
Vol 296 (4) ◽  
pp. C857-C867 ◽  
Author(s):  
Silvia M. Uriarte ◽  
Neelakshi R. Jog ◽  
Gregory C. Luerman ◽  
Samrath Bhimani ◽  
Richard A. Ward ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Human Neutrophils ◽  
Functional Responses ◽  
Membrane Expression ◽  
Granule Exocytosis ◽  
Plasma Membrane Expression ◽  
Microtubular Cytoskeleton ◽  
Latrunculin A ◽  
Azurophil Granule

We have recently reported that disruption of the actin cytoskeleton enhanced N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated granule exocytosis in human neutrophils but decreased plasma membrane expression of complement receptor 1 (CR1), a marker of secretory vesicles. The present study was initiated to determine if reduced CR1 expression was due to fMLP-stimulated endocytosis, to determine the mechanism of this endocytosis, and to examine its impact on neutrophil functional responses. Stimulation of neutrophils with fMLP or ionomycin in the presence of latrunculin A resulted in the uptake of Alexa fluor 488-labeled albumin and transferrin and reduced plasma membrane expression of CR1. These effects were prevented by preincubation of the cells with sucrose, chlorpromazine, or monodansylcadaverine (MDC), inhibitors of clathrin-mediated endocytosis. Sucrose, chlorpromazine, and MDC also significantly inhibited fMLP- and ionomycin-stimulated specific and azurophil granule exocytosis. Disruption of microtubules with nocodazole inhibited endocytosis and azurophil granule exocytosis stimulated by fMLP in the presence of latrunculin A. Pharmacological inhibition of phosphatidylinositol 3-kinase, ERK1/2, and PKC significantly reduced fMLP-stimulated transferrin uptake in the presence of latrunculin A. Blockade of clathrin-mediated endocytosis had no significant effect on fMLP-stimulated phosphorylation of ERK1/2 in neutrophils pretreated with latrunculin A. From these data, we conclude that the actin cytoskeleton functions to limit microtubule-dependent, clathrin-mediated endocytosis in stimulated human neutrophils. The limitation of clathrin-mediated endocytosis by actin regulates the extent of both specific and azurophilic granule exocytosis.

scholarly journals Cortical Granule Exocytosis Is Mediated by Alpha-SNAP and N-Ethilmaleimide Sensitive Factor in Mouse Oocytes

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135679 ◽  
Author(s):  
Matilde de Paola ◽  
Oscar Daniel Bello ◽  
Marcela Alejandra Michaut
Keyword(s):  
Cortical Granule ◽  
Granule Exocytosis ◽  
Mouse Oocytes ◽  
Sensitive Factor ◽  
Cortical Granule Exocytosis

scholarly journals Plasma Membrane Order Regulates Insulin Granule Exocytosis

2020 ◽  
Vol 118 (3) ◽  
pp. 401a-402a
Author(s):  
Chase Amos ◽  
Noah Schenk ◽  
Volker Kiessling ◽  
Alex J. Kreutzberger ◽  
Weronika Tomaka ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Granule Exocytosis ◽  
Membrane Order ◽  
Insulin Granule

scholarly journals Primary granule exocytosis in human neutrophils is regulated by Rac-dependent actin remodeling

2008 ◽  
Vol 295 (5) ◽  
pp. C1354-C1365 ◽  
Author(s):  
Troy Mitchell ◽  
Andrea Lo ◽  
Michael R. Logan ◽  
Paige Lacy ◽  
Gary Eitzen
Keyword(s):  
Actin Polymerization ◽  
Microscopic Analysis ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Cell Cortex ◽  
Secretory Cells ◽  
Actin Remodeling ◽  
Granule Exocytosis ◽  
Primary Granule

The actin cytoskeleton regulates exocytosis in all secretory cells. In neutrophils, Rac2 GTPase has been shown to control primary (azurophilic) granule exocytosis. In this report, we propose that Rac2 is required for actin cytoskeletal remodeling to promote primary granule exocytosis. Treatment of neutrophils with low doses (≤10 μM) of the actin-depolymerizing drugs latrunculin B (Lat B) or cytochalasin B (CB) enhanced both formyl peptide receptor- and Ca2+ionophore-stimulated exocytosis. Higher concentrations of CB or Lat B, or stabilization of F-actin with jasplakinolide (JP), inhibited primary granule exocytosis measured as myeloperoxidase release but did not affect secondary granule exocytosis determined by lactoferrin release. These results suggest an obligatory role for F-actin disassembly before primary granule exocytosis. However, lysates from secretagogue-stimulated neutrophils showed enhanced actin polymerization activity in vitro. Microscopic analysis showed that resting neutrophils contain significant cortical F-actin, which was redistributed to sites of primary granule translocation when stimulated. Exocytosis and actin remodeling was highly polarized when cells were primed with CB; however, polarization was reduced by Lat B preincubation, and both polarization and exocytosis were blocked when F-actin was stabilized with JP. Treatment of cells with the small molecule Rac inhibitor NSC23766 also inhibited actin remodeling and primary granule exocytosis induced by Lat B/fMLF or CB/fMLF, but not by Ca2+ionophore. Therefore, we propose a role for F-actin depolymerization at the cell cortex coupled with Rac-dependent F-actin polymerization in the cell cytoplasm to promote primary granule exocytosis.

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