Regulation of polymorphonuclear leukocyte degranulation and oxidant production by ceramide through inhibition of phospholipase D

Mansfield, Pamela J.; Hinkovska‐Galcheva, Vania; Carey, Shannon S.; Shayman, James A.; Boxer, Laurence A.

doi:10.1182/blood.v99.4.1434

Cited by 27 publications

(27 citation statements)

References 52 publications

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“…Previous studies by us and others 1,3,19 have demonstrated C 2 -ceramide inhibition of PLD activity. However, many of these studies involved cell-free systems, wherein some functions cannot be assayed, or receptor-mediated PLD activation, in which parallel pathways may also be activated and confound the signaling model.…”

Section: Resultsmentioning

confidence: 68%

“…In the latter studies, 10 M C 2 -ceramide was adequate to inhibit degranulation. 1 In the permeabilized PMNs, 50 M C 2 -ceramide was required. To evaluate possible nonspecific interactions between C 2 -ceramide and streptolysin O, we measured C 2 -ceramide in membrane and cytosol fractions of intact and streptolysin O-permeabilized PMNs after incubations.…”

Section: Resultsmentioning

confidence: 99%

“…We and others have demonstrated that PMN phagocytosis, degranulation, and oxidant production are regulated by phospholipase D (PLD). [1][2][3][4][5][6][7] PLD produces phosphatidic acid (PA) which may act directly as a second messenger or be converted to diacylglycerol (DAG) by phosphatidate phosphohydrolase. DAG activates protein kinase C (PKC) 8 and may contribute to granule-membrane fusion.…”

Section: Introductionmentioning

confidence: 99%

“…The exogenous addition of the cell-permeable analog C 2 -ceramide has been shown to inhibit phagocytosis, degranulation, and oxidant production in PMNs through its inhibition of PLD activity. 1,3 The inhibition of PLD by ceramide is well established [17][18][19] ; however, the mechanism of inhibition has not been defined. Others have found C 2 -ceramide to inhibit ARF and RhoA translocation to the plasma membrane in HL-60 cells.…”

Section: Introductionmentioning

confidence: 99%

“…Cytosol and plasma membrane fractions were separated as described previously. 1 Briefly, samples were ultracentrifuged over discontinuous 15% and 35% sucrose gradients. Plasma membrane fractions were taken from the 15% 35% interface, then pelleted.…”

Section: Pld Activity In Cell-free Systemmentioning

confidence: 99%

See 4 more Smart Citations

Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPγS-stimulated polymorphonuclear leukocytes

Mansfield

Carey

Hinkovska‐Galcheva

et al. 2004

Blood

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Pld Activity In Cell-free Systemmentioning

confidence: 99%

See 3 more Smart Citations

Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPγS-stimulated polymorphonuclear leukocytes

Mansfield

Carey

Hinkovska‐Galcheva

et al. 2004

Blood

Self Cite

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The superoxide-generating NADPH oxidase: structural aspects and activation mechanism

Vignais¹

2002

Cellular and Molecular Life Sciences (CMLS)

694

597

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Flavocytochrome b558 is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of O2 into the superoxide anion O2 in phagocytic cells. Flavocytochrome b558 is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox forphagocyte oxidase) (beta subunit) and a small protein p22phox (alpha subunit). The other components of the respiratory-burst oxidase are water-soluble proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound flavocytochrome b558 which becomes activated and generates O2-. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a genetic disorder characterized by severe and recurrent infections, illustrating the role of O2- and the derived metabolites H2O2 and HOCl in host defense against invading microorganisms. The electron carriers, FAD and hemes b, and the binding site for NADPH are confined to the gp91phox subunit of flavocytochrome b558. The p22phox subunit serves as a docking site for the cytoso lic phox proteins. This review provides an overview of current knowledge on the structural organization of the O2(-)-generating flavocytochrome b558, its kinetics, its mechanism of activation and the regulation of its biosynthesis. Homologues of gp91phox, called Nox and Duox, are present in a large variety of non-phagocytic cells. They exhibit modest O2(-)-generating oxidase activity, and some act as proton channels. Their role in various aspects of signal transduction is currently under investigation and is briefly discussed.

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Protein kinase C and phospholipase D: intimate interactions in intracellular signaling

Becker

Hannun

2005

CMLS, Cell. Mol. Life Sci.

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Diacylglycerol (DAG) was discovered as a potent lipid second messenger with protein kinase C (PKC) as its major cellular target more than 25 years ago. There is increasing evidence of significant complexity within lipid signaling, and the classical DAG-PKC model no longer stands alone but is part of a larger bioactive lipid universe involving glycerolipids and sphingolipids. Multiple layers of regulation exist among PKC- and DAG-metabolizing enzymes such as phosphatidylcholine (PC)-specific phospholipase D, and cross-talk exists between the glycerolipid and sphingolipid pathways, with PKC at the center. Currently, there is intense interest in the question of whether DAG derived from PC can function as a lipid second messenger and regulate PKC analogous to DAG derived from phosphatidylinositol-4,5-bisphosphate (PIP2). To address these issues and incorporate DAG-PKC and other signaling pathways into an expanded view of cell biology, it will be necessary to go beyond the classical approaches and concepts.

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Regulation of polymorphonuclear leukocyte degranulation and oxidant production by ceramide through inhibition of phospholipase D

Cited by 27 publications

References 52 publications

Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPγS-stimulated polymorphonuclear leukocytes

Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPγS-stimulated polymorphonuclear leukocytes

The superoxide-generating NADPH oxidase: structural aspects and activation mechanism

Protein kinase C and phospholipase D: intimate interactions in intracellular signaling

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