Involvement of Phosphatidic Acid in both Degranulation and Oxidative Activity in fMet-Leu-Phe Stimulated Polymorphonuclear Leukocytes

Vocks, Andreas; Petković, Marijana; Arnhold, Jürgen

doi:10.1159/000071867

Cited by 12 publications

(6 citation statements)

References 40 publications

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“…3). Our results are supported by other studies showing that degranulation by CXCL8 or other mediators is also dependent on PI3K activation (55‐57). In PMN the PI3K pathway is separate from Ca 2+ mobilization because wortmannin does not influence the rise in intracellular Ca 2+ after stimulation with CXCL8 (23, 24), and Ca 2+ mobilization after leukotriene B4 stimulation is not reduced in PI3Kγ KO mice (24).…”

Section: Discussionsupporting

confidence: 91%

Pain control by CXCR2 ligands through Ca²⁺‐regulated release of opioid peptides from polymorphonuclear cells

Rittner¹,

Łabuz²,

Mousa³

et al. 2006

FASEB j.

113

116

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Leukocytes counteract inflammatory pain by releasing opioid peptides, which bind to opioid receptors on peripheral sensory neurons. In the early phase of inflammation, polymorphonuclear cells (PMN) are the major source of opioids. Their recruitment is governed by ligands at the chemokine receptor CXCR2. Here, we examined whether chemokines can also induce opioid peptide secretion from PMN and thus inhibit inflammatory pain. In rats with hindpaw inflammation, intraplantar injection of CXCL2/3, but not of the CXCR4 ligand CXCL12, elicited naloxone-reversible (i.e., opioid receptor mediated) mechanical and thermal analgesia, which was abolished by systemic PMN depletion. Both CXCR1/2- and CXCR4-ligands induced PMN chemotaxis, but only CXCR1/2 ligands triggered opioid release from human and rat PMN in vitro. This release was unaltered by extracellular Ca2+ chelation, was mimicked by thapsigargin and was blocked by inhibitors of the inositol 1,4,5-triphosphate receptor (IP3) and by intracellular Ca2+ chelation, indicating that it required Ca2+ from intracellular but not extracellular sources. Furthermore, release was partially reduced by phosphoinositol-3-kinase (PI3K) inhibitors. Adoptive transfer of allogenic PMN into PMN-depleted rats reconstituted CXCL2/3-induced analgesia, which was inhibited by prior ex vivo chelation of intracellular Ca2+. These findings demonstrate that, beyond cell recruitment, CXCR2 ligands induce Ca2+-regulated opioid release from PMN and thereby inhibit inflammatory pain in vivo.

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Section: Discussionsupporting

confidence: 91%

Pain control by CXCR2 ligands through Ca²⁺‐regulated release of opioid peptides from polymorphonuclear cells

Rittner¹,

Łabuz²,

Mousa³

et al. 2006

FASEB j.

113

116

View full text Add to dashboard Cite

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“…This result is also in agreement with the inhibition by secinH3 of MPO, lactoferrin, and MMP9 secretion, which are selective markers of primary, secondary, and tertiary granules, respectively. 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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“…A study by Hills indicates that alterations in phospholipid composition and concentrations are associated with the development of OA 23 . Phospholipids and enzymes involved in lipid metabolism were demonstrated to affect the regulation of the signaling steps leading to neutrophil activation 24,25 . In addition, lysophosphatidylcholine (LPC) plays an important role in inflammation 26 .…”

Section: Rheumatologymentioning

confidence: 99%

Relationship Between Blood Plasma and Synovial Fluid Metabolite Concentrations in Patients with Osteoarthritis

Zhang

Likhodii²,

Aref‐Eshghi³

et al. 2015

J Rheumatol

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Involvement of Phosphatidic Acid in both Degranulation and Oxidative Activity in fMet-Leu-Phe Stimulated Polymorphonuclear Leukocytes

Cited by 12 publications

References 40 publications

Pain control by CXCR2 ligands through Ca²⁺‐regulated release of opioid peptides from polymorphonuclear cells

Pain control by CXCR2 ligands through Ca²⁺‐regulated release of opioid peptides from polymorphonuclear cells

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

Relationship Between Blood Plasma and Synovial Fluid Metabolite Concentrations in Patients with Osteoarthritis

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Involvement of Phosphatidic Acid in both Degranulation and Oxidative Activity in fMet-Leu-Phe Stimulated Polymorphonuclear Leukocytes

Cited by 12 publications

References 40 publications

Pain control by CXCR2 ligands through Ca2+‐regulated release of opioid peptides from polymorphonuclear cells

Pain control by CXCR2 ligands through Ca2+‐regulated release of opioid peptides from polymorphonuclear cells

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

Relationship Between Blood Plasma and Synovial Fluid Metabolite Concentrations in Patients with Osteoarthritis

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Product

Resources

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Pain control by CXCR2 ligands through Ca²⁺‐regulated release of opioid peptides from polymorphonuclear cells

Pain control by CXCR2 ligands through Ca²⁺‐regulated release of opioid peptides from polymorphonuclear cells