scholarly journals Arachidonic acid activates phospholipase D in human neutrophils; essential role of endogenous leukotriene B4and inhibition by adenosine A2Areceptor engagement

2003 ◽  
Vol 73 (4) ◽  
pp. 530-539 ◽  
Author(s):  
Sonya Grenier ◽  
Nicolas Flamand ◽  
Julie Pelletier ◽  
Paul H. Naccache ◽  
Pierre Borgeat ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase D ◽  
Essential Role ◽  
Human Neutrophils

scholarly journals Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier

2007 ◽  
Vol 293 (2) ◽  
pp. F501-F505 ◽  
Author(s):  
Jan Michael Williams ◽  
Mukut Sharma ◽  
Siddam Anjaiahh ◽  
John R. Falck ◽  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Essential Role ◽  
Dienoic Acid ◽  
Permeability Barrier ◽  
Selective Inhibitors ◽  
Glomerular Permeability ◽  
Isolated Glomeruli ◽  
Cytochrome P 450 ◽  
Protein Permeability

This study examined the metabolism of arachidonic acid (AA) by cytochrome P-450 enzymes in isolated glomeruli and the effects of selective inhibitors of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatetraenoic acids (EETs) on glomerular permeability to albumin ( Palb). Glomeruli avidly produced 20-HETE, EETs, dihydroxyeicosatetraenoic acids (diHETEs), and HETEs when incubated with exogenous AA. N-hydroxy- N′-(4-butyl-2-methylphenyl)formamidine (HET0016; 10 μM) selectively inhibited the formation of 20-HETE by 95% and increased Palb from 0.00 ± 0.08 to 0.73 ± 0.10 ( n = 43 glomeruli, 4 rats). Addition of a 20-HETE mimetic, 20-hydroxyeicosa-5( Z),14( Z)-dienoic acid (20-5,14-HEDE; 1 μM) opposed the effects of HET0016 (10 μM) to increase Palb (0.21 ± 0.10, n = 36 glomeruli, 4 rats). Preincubation of glomeruli with exogenous AA to increase basal production of 20-HETE had a similar effect. We also examined the effect of an epoxygenase inhibitor, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MSPPOH; 5 μM), on Palb. MSPPOH (5 μM) significantly increased Palb but had no effect on the synthesis of EETs in glomeruli incubated with AA. However, MSPPOH (5 μM) selectively reduced epoxygenase activity by 50% in glomeruli incubated without added AA. Pretreatment with 8,9-EET (100 nM) attenuated the effects of MSPPOH (5 μM) on Palb. These results indicate that glomeruli produce 20-HETE, EETs, diHETEs, and HETEs and that endogenously formed 20-HETE and EETs play an essential role in the maintenance of the glomerular permeability barrier to albumin.

scholarly journals Neutrophil activation by anti-proteinase 3 antibodies in Wegener's granulomatosis: role of exogenous arachidonic acid and leukotriene B4 generation.

1996 ◽  
Vol 184 (4) ◽  
pp. 1567-1572 ◽  
Author(s):  
F Grimminger ◽  
K Hattar ◽  
C Papavassilis ◽  
B Temmesfeld ◽  
E Csernok ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Wegener’S Granulomatosis ◽  
Wegener's Granulomatosis ◽  
Neutrophil Activation ◽  
Tnf Alpha ◽  
Lipid Mediator ◽  
Human Neutrophils ◽  
Proteinase 3 ◽  
Lipoxygenase Pathway

Among the anti-neutrophil cytoplasmic antibodies (ANCA), those targeting proteinase 3 (PR3) have a high specificity for Wegener's granulomatosis (WG). It is known that a preceding priming of neutrophils with cytokines is a prerequisite for membrane surface expression of PR3, which is then accessible to autoantibody binding. Employing a monoclonal antibody directed against human PR3 and ANCA-positive serum from WG patients with specificity for PR3, we now investigated the role of free arachidonic acid (AA) in autoantibody-related human neutrophil activation. Priming of neutrophils with tumor necrosis factor (TNF-alpha) for 15 min or exposure to anti-PR3 antibodies or incubation with free AA (10 microM) as sole events did not provoke superoxide generation, elastase secretion or generation of 5-lipoxygenase products of AA. Similarly, the combination of TNF-alpha-priming and AA incubation was ineffective. When TNF-alpha-primed neutrophils were stimulated by anti-PR3 antibodies, superoxide and elastase secretion was provoked in the absence of lipid mediator generation. However, when free AA was additionally provided, a strong activation of the 5-lipoxygenase pathway was demasked, with the appearance of excessive quantities of leukotriene (LT)B4, LTA4, and 5-hydroxyeicosatetraenoic acid. Moreover, superoxide and elastase secretion were markedly amplified, and studies with 5-lipoxygenase inhibitors and a LTB4-antagonist demonstrated this was due to an LTB4-related autocrine loop of cell activation. In contrast, the increased synthesis of platelet-activating factor in response to TNF-alpha-priming and anti-PR3 stimulation did not contribute to the amplification loop of neutrophil activation under the given conditions. We conclude that anti-PR3 antibodies are potent inductors of the 5-lipoxygenase pathway in primed human neutrophils, and extracellular free AA, as provided at an inflammatory focus, synergizes with the autoantibodies to evoke full-blown lipid mediator generation, granule secretion and respiratory burst. Such events may be enrolled in the pathogenesis of focal necrotizing vascular injury in Wegener's granulomatosis.

An essential role for phospholipase D in the recruitment of vesicle amine transport protein-1 to membranes in human neutrophils

2011 ◽  
Vol 81 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Delphine Faugaret ◽  
François C. Chouinard ◽  
Danielle Harbour ◽  
Mohammed-Amine El azreq ◽  
Sylvain G. Bourgoin
Keyword(s):  
Phospholipase D ◽  
Essential Role ◽  
Transport Protein ◽  
Human Neutrophils

scholarly journals Phospholipase D activity is essential for actin localization and actin-based motility in Dictyostelium

2005 ◽  
Vol 389 (1) ◽  
pp. 207-214 ◽  
Author(s):  
Soha ZOUWAIL ◽  
Trevor R. PETTITT ◽  
Stephen K. DOVE ◽  
Margarita V. CHIBALINA ◽  
Dale J. POWNER ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Essential Role ◽  
Kinase Activity ◽  
Complete Loss ◽  
Complete Inhibition ◽  
Cellular Processes ◽  
Small Clusters ◽  
Actin Localization

PLD (phospholipase D) activity catalyses the generation of the lipid messenger phosphatidic acid, which has been implicated in a number of cellular processes, particularly the regulation of membrane traffic. In the present study, we report that disruption of PLD signalling causes unexpectedly profound effects on the actin-based motility of Dictyostelium. Cells in which PLD activity is inhibited by butan-1-ol show a complete loss of actin-based structures, accompanied by relocalization of F-actin into small clusters, and eventually the nucleus, without a visible fall in levels of F-actin. Addition of exogenous phosphatidic acid reverses the effects of butan-1-ol, confirming that these effects are caused by inhibition of PLD. Loss of motility correlates with complete inhibition of endocytosis and a reduction in phagocytosis. Inhibition of PLD caused a major decrease in the synthesis of PtdIns(4,5)P2, which could again be reversed by exogenously applied phosphatidic acid. Thus the essential role of PLD signalling in both motility and endocytosis appears to be mediated directly via regulation of PtdIns(4)P kinase activity. This implies that localized PLD-regulated synthesis of PtdIns(4,5)P2 is essential for Dictyostelium actin function.

Role of cytochrome b-559 in arachidonic acid activation of resting human neutrophils

1988 ◽  
Vol 944 (3) ◽  
pp. 437-443 ◽  
Author(s):  
Norma Amit ◽  
Trung Pham Huu ◽  
Patrick Sourbier ◽  
Claude Marquetty ◽  
Jacques Hakim
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome B ◽  
Human Neutrophils ◽  
Acid Activation
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