The actin cytoskeleton regulates exocytosis of all neutrophil granule subsets

Jog, Neelakshi R.; Rane, Madhavi J.; Lominadze, George; Luerman, Gregory C.; Ward, Richard A.; McLeish, Kenneth R.

doi:10.1152/ajpcell.00384.2006

Cited by 108 publications

(122 citation statements)

References 49 publications

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“…Cytochalasin B and similar compounds disrupt the actin cytoskeleton, facilitating the release of cytoplasmic granules. Much like our results, the in vitro release of azurophilic granules that contain ␣-defensins from fMLP-stimulated PMN require the presence of an actin cytoskeleton-disrupting agent (47). Therefore, the question that arises is what could substitute for cytochalasin B priming in the in vivo setting?…”

Section: Discussionsupporting

confidence: 61%

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

Flamand

Tremblay

Borgeat

2007

The Journal of Immunology

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Leukotriene B4 (LTB4) is a bioactive lipid derived from the metabolism of arachidonic acid. Mainly produced by polymorphonuclear leukocytes (PMN) and macrophages, LTB4 triggers several functional responses important in host defense, including the secretion of lysosomal enzymes, the activation of NADPH oxidase activity, NO formation, and phagocytosis. We report that LTB4, but not structural analogs thereof, stimulates primed human PMN to release molecules having potent antimicrobial activities. Exposure of bacteria (Escherichia coli and Staphylococcus aureus) or viruses (herpes simplex virus type 1 and HIV type 1) to supernatants of LTB4-activated PMN lead to ≥90% reduction in infectivity. ELISA and mass spectroscopy analysis of proteins released from LTB4-activated PMN have identified several antimicrobial proteins, including α-defensins, cathepsin G, elastase, lysozyme C, and LL-37, that are likely to participate in the killing of microorganisms. In addition to these in vitro observations, i.v. injections of LTB4 (50 μg/kg) to monkeys led to an increase in α-defensin plasmatic levels and enhanced ex vivo antimicrobial activities of plasma. These results demonstrate the ability of LTB4 to cause the release of potent antimicrobial agents from PMN in vitro as well as in vivo and add further support to the important role of LTB4 in host defense.

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Section: Discussionsupporting

confidence: 61%

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

Flamand

Tremblay

Borgeat

2007

The Journal of Immunology

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“…The mechanisms involved in neutrophil degranulation are dependent on several factors such as the PKC activation pathway, intracellular Ca 2+ and the actin cytoskeleton. Jog et al (36) reported that the actin cytoskeleton restricts azurophil granule access to the plasma membrane under both basal and stimulated conditions to prevent the release of destructive enzymes such as myeloperoxidase. Studies have reported that some polyphenolic compounds, such as flavonoids, may disturb the degranulation process of the phagocytic cell by interacting with receptors on the cell membrane (37), inhibiting intracellular Ca 2+ elevation via a reduction in phospholipase-C activity (1,3) and by inhibiting PKC (by blocking the ATP binding site on the catalytic unit of PKC, for example) (13,38,39).…”

Section: Discussionmentioning

confidence: 99%

Modulatory activities of Agelanthus dodoneifolius (Loranthaceae) extracts on stimulated equine neutrophils and myeloperoxidase activity

Boly¹,

Dessy²,

Kohnen³

et al. 2011

Int J Mol Med

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Abstract. Agelanthus dodoneifolius DC Danser (Loranthaceae)is used for the treatment of various diseases including asthma. The aqueous and hydroalcoholic extracts have been reported to have anti-inflammatory, spasmolytic and bronchorelaxant activities. The present study investigates the effects of the aqueous decoction and the diethyl ether, ethyl acetate and butanolic fractions of Agelanthus dodoneifolius DC Danser (Loranthaceae) on reactive oxygen species (ROS) production and myeloperoxidase (MPO) release by phorbol 12-myristate 13-acetate (PMA)-stimulated equine neutrophils and on purified equine MPO activity. ROS production and MPO release by the PMA-stimulated neutrophils were measured by the lucigenin-enhanced chemiluminescence and ELISA assays, respectively. Specific immunological extraction followed by enzymatic detection (SIEFED) was used to specifically measure the equine MPO activity. Identification and quantification of the individual and total phenolic and flavonoid compounds were performed using UPLC-MS/MS equipment and colorimetric methods involving Folin-Ciocalteu and AlCl 3 , respectively. All the tested extracts displayed dose-dependent inhibitory effects on the oxidant activities of neutrophils; a stronger effect was observed with the organic fractions than the aqueous decoction. These findings could be correlated with a high content of phenolic and flavonoid compounds. The results confirm the previously shown anti-inflammatory effect of Agelanthus dodoneifolius and its potential use for the treatment of neutrophil-dependent inflammatory diseases. IntroductionPolymorphonuclear neutrophils (PMNs) are the primary effector cells in host responses to injury and infection (1-4). The antimicrobial function of stimulated PMNs is based on their phagocytic capacity and their ability to release oxidant and proteolytic enzymes as well as reactive oxygen species (ROS) involved in the destruction of microorganisms. ROS play important roles in the pathogenesis of various serious diseases, such as neurodegenerative disorders, aging, cancer, cataracts, inflammation and cardiovascular diseases including atherosclerosis (5,6).Myeloperoxidase (MPO), a heme peroxidase enzyme stored in the azurophilic granules of neutrophils, plays a crucial role in the destruction of bacteria inside PMNs. The bacterial killing process mainly uses hydrogen peroxide (H 2 O 2 ) and the chloride anion (Cl -) to produce hypochlorous

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“…The molecular mechanism by which cytohesin-1 regulates granule secretion remains to be studied, but a potential explanation may be provided by inhibition of the production of fusogenic lipids, such as PLD-derived PA (77) and/or the remodeling of the actin cytoskeleton (61). Indeed, the actin cytoskeleton regulates the secretion of several PMN granules (78), and a direct association of cytohesin-1 with the actin cytoskeleton has already been reported (54).…”

Section: Discussionmentioning

confidence: 99%

Cytohesin-1 Regulates the Arf6-Phospholipase D Signaling Axis in Human Neutrophils: Impact on Superoxide Anion Production and Secretion

Azreq

Garceau

Harbour

et al. 2009

The Journal of Immunology

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Polymorphonuclear neutrophil (PMN) stimulation with fMLP stimulates small G proteins such as ADP-ribosylation factors (Arfs) Arf1 and Arf6, leading to phospholipase D (PLD) activation and functions such as degranulation and the oxidative burst. However, the molecular links between fMLF receptors and PLD remain unclear. PMNs express cytohesin-1, an Arf-guanine exchange factor that activates Arfs, and its expression is strongly induced during the acquisition of the neutrophilic phenotype by neutrophil-like cells. The role of cytohesin-1 in the activation of the fMLF-Arf-PLD signaling axis, and the accomplishment of superoxide anion production, and degranulation was investigated in PMNs using the selective inhibitor of cytohesin, Sec 7 inhibitor H3 (secinH3). Cytohesin-1 inhibition with secinH3 leads to Arf6 but not Arf1 inhibition, demonstrating the specificity for Arf6, and fMLF-mediated activation of PLD and of the oxidative burst as well. We observed a decrease in fMLF-mediated protein secretion and expression of cell surface markers corresponding to primary (CD63/myeloperoxidase), secondary (CD66/lactoferrin), and tertiary (matrix metalloproteinase-9) granules in PMNs incubated with secinH3. Similarly, silencing cytohesin-1 or Arf6 in PLB-985 cells negatively affected fMLF-induced activation of PLD, superoxide production, and expression of granule markers on the cell surface. In contrast, stable overexpression of cytohesin-1 in PLB-985 cells enhanced fMLF-induced activation of Arf6, PLD, and NADPH oxidase. The results of this study provide evidence for an involvement of cytohesin-1 in the regulation of the functional responses of human PMNs and link these events, in part at least, to the activation of Arf6.

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The actin cytoskeleton regulates exocytosis of all neutrophil granule subsets

Cited by 108 publications

References 49 publications

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

Modulatory activities of Agelanthus dodoneifolius (Loranthaceae) extracts on stimulated equine neutrophils and myeloperoxidase activity

Cytohesin-1 Regulates the Arf6-Phospholipase D Signaling Axis in Human Neutrophils: Impact on Superoxide Anion Production and Secretion

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