Endothelial-secreted arachidonic acid metabolites modulate polymorphonuclear leukocyte chemotaxis and diapedesis in vitro

Abstract The influence of endothelial cells (ECs) on polymorphonuclear leukocyte (PMN) motility was examined using in vitro assays of PMN diapedesis and chemotaxis. ECs are seen to release arachidonic acid (20:4) metabolites that directly increase or decrease PMN movement, with their general effect being enhanced motility. This effect can be increased or decreased by treating ECs with stimulators or inhibitors of 20:4 metabolism, respectively. The metabolites include thromboxane B2, which increases PMN random motility, chemotaxis, and diapedesis in a dose- responsive manner and which acts as a chemoattractant; 6-keto-PGF1 alpha, which increases chemotaxis and diapedesis at high doses but decreases these responses at low doses; and a lipoxygenase-derived metabolite, suggested to be 5-hydroxyeicosatetraenoic acid, which increases chemotaxis and diapedesis. Thromboxane A2 and prostacyclin mimetics also affect chemotaxis in qualitatively similar manners as TxB2 and 6-keto-PGF1 alpha, respectively, but display greater potency. EC release of these metabolites is also seen to be substratum modulated, with an increased production by cells cultured on extracellular matrices. These results suggest that ECs are capable of modulating PMN motility and suggest a role for ECs in the control of PMN diapedesis.

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Endothelial-secreted arachidonic acid metabolites modulate polymorphonuclear leukocyte chemotaxis and diapedesis in vitro

Blood ◽

10.1182/blood.v71.3.771.bloodjournal713771 ◽

1988 ◽

Vol 71 (3) ◽

pp. 771-779

Author(s):

J Doukas ◽

HB Hechtman ◽

D Shepro

Keyword(s):

Arachidonic Acid ◽

Polymorphonuclear Leukocyte ◽

Thromboxane A2 ◽

In Vitro Assays ◽

General Effect ◽

Random Motility ◽

Acid Metabolites ◽

Leukocyte Chemotaxis ◽

High Doses

The influence of endothelial cells (ECs) on polymorphonuclear leukocyte (PMN) motility was examined using in vitro assays of PMN diapedesis and chemotaxis. ECs are seen to release arachidonic acid (20:4) metabolites that directly increase or decrease PMN movement, with their general effect being enhanced motility. This effect can be increased or decreased by treating ECs with stimulators or inhibitors of 20:4 metabolism, respectively. The metabolites include thromboxane B2, which increases PMN random motility, chemotaxis, and diapedesis in a dose- responsive manner and which acts as a chemoattractant; 6-keto-PGF1 alpha, which increases chemotaxis and diapedesis at high doses but decreases these responses at low doses; and a lipoxygenase-derived metabolite, suggested to be 5-hydroxyeicosatetraenoic acid, which increases chemotaxis and diapedesis. Thromboxane A2 and prostacyclin mimetics also affect chemotaxis in qualitatively similar manners as TxB2 and 6-keto-PGF1 alpha, respectively, but display greater potency. EC release of these metabolites is also seen to be substratum modulated, with an increased production by cells cultured on extracellular matrices. These results suggest that ECs are capable of modulating PMN motility and suggest a role for ECs in the control of PMN diapedesis.

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In Vitro Incorporation and Metabolism of Icosapentaenoic and Docosahexaenoic Acids in Human Platelets - Effect on Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661603 ◽

1986 ◽

Vol 56 (01) ◽

pp. 057-062 ◽

Cited By ~ 56

Author(s):

Martine Croset ◽

M Lagarde

Keyword(s):

Arachidonic Acid ◽

Fatty Acid ◽

Platelet Aggregation ◽

Fatty Acid Distribution ◽

Thromboxane A2 ◽

Human Platelets ◽

Aggregation Response ◽

Docosahexaenoic Acids ◽

Membrane Level

SummaryWashed human platelets were pre-loaded with icosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or EPA + DHA and tested for their aggregation response in comparison with control platelets. In fatty acid-rich platelets, an inhibition of the aggregation could be observed when induced by thrombin, collagen or U-46619. The strongest inhibition was observed with DHA-rich platelets and it was reduced when DHA was incorporated in the presence of EPA.Study of fatty acid distribution in cell lipids after loading showed that around 90% of EPA or DHA taken up was acylated into phospholipids and a very small amount (less than 2%) remained in their free and hydroxylated forms. DHA was more efficiently acylated into phosphatidylethanolamine (PE) than into phosphatidylinositol (PI) in contrast to what observed with EPA, and both acids were preferentially incorporated into phosphatidylcholine (PC). EPA inhibited total incorporation of DHA and increased its relative acylation into PE at the expense of PC. In contrast, DHA did not affect the acylation of EPA. Upon stimulation with, thrombin, EPA was liberated from phospholipids and oxygenated (as judged by the formation of its monohydroxy derivative) whereas DHA was much less metabolized, although consistently transferred into PE.It is concluded that EPA and DHA might affect platelet aggregation via different mechanisms when pre-loaded in phospholipids. Whereas EPA is known to alter thromboxane A2 metabolism from endogenous arachidonic acid, by competing with it, DHA might act directly at the membrane level for inhibiting aggregation.

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The Effect of Arachidonic Acid Metabolites on the Ciliary Beat Frequency of Human Nasal Mucosa in Vitro

Acta Oto-Laryngologica ◽

10.3109/00016489209137462 ◽

1992 ◽

Vol 112 (4) ◽

pp. 697-702 ◽

Cited By ~ 14

Author(s):

Steve R. Bonin ◽

P. Perry Phillips ◽

Thomas V. McCaffrey

Keyword(s):

Arachidonic Acid ◽

Nasal Mucosa ◽

Beat Frequency ◽

Ciliary Beat Frequency ◽

Human Nasal Mucosa ◽

Arachidonic Acid Metabolites ◽

Acid Metabolites ◽

Ciliary Beat

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Arachidonic acid metabolites induced β-adrenoceptor densitization in rat lung in vitro

Prostaglandins ◽

10.1016/0090-6980(85)90008-5 ◽

1985 ◽

Vol 30 (5) ◽

pp. 799-809 ◽

Cited By ~ 8

Author(s):

Luisa Daffonchio ◽

Maria Pia Abbracchio ◽

Alicia Hernandez ◽

Emanuela Giani ◽

Flaminio Cattabeni ◽

...

Keyword(s):

Arachidonic Acid ◽

Rat Lung ◽

Arachidonic Acid Metabolites ◽

Acid Metabolites

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Induction of Suppressor T Cells in Vitro by Arachidonic Acid Metabolites Issued from the Lipoxygenase Pathway

Prostaglandins, Leukotrienes, and Lipoxins ◽

10.1007/978-1-4684-4946-4_54 ◽

1985 ◽

pp. 565-575 ◽

Cited By ~ 1

Author(s):

Norbert Gualde ◽

James S. Goodwin

Keyword(s):

T Cells ◽

Arachidonic Acid ◽

Suppressor T Cells ◽

Lipoxygenase Pathway ◽

Arachidonic Acid Metabolites ◽

Acid Metabolites

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Control of gap junction formation in canine trachea by arachidonic acid metabolites

AJP Cell Physiology ◽

10.1152/ajpcell.1986.250.3.c495 ◽

1986 ◽

Vol 250 (3) ◽

pp. C495-C505 ◽

Cited By ~ 33

Author(s):

R. Agrawal ◽

E. E. Daniel

Keyword(s):

Arachidonic Acid ◽

Gap Junctions ◽

Gap Junction ◽

Direct Effects ◽

Leukotriene C4 ◽

Lipoxygenase Pathway ◽

Junction Formation ◽

Acid Metabolites ◽

Pg E2

This study examined whether the synthesis of the metabolites of arachidonic acid (AA) was involved in gap junction formation by 4-aminopyridine (4-AP) treatment in vitro in canine trachealis. Studies were made of the effects on gap junction formation of putative inhibitors of the cyclooxygenase and of both this and the lipoxygenase pathway of AA metabolism and the direct effects of prostaglandins (PG) E2 and I2. The number of gap junctions of similar size was increased after brief exposure to 4-AP. After indomethacin (IDM), 4-AP treatment decreased the number of gap junctions but did not affect their size. Pretreatment with 5,8,11,14-eicosatetraynoic acid or nordihydroguiaretic acid, putative inhibitors of cyclooxygenase and lipoxygenase enzymes, inhibited both the 4-AP-induced increase and decrease in the number of gap junctions. FPL 55712, a putative antagonist of leukotriene C4, did not alter either the number or the size of gap junctions when added alone or in combination with IDM. AA alone increased the number of gap junctions, but after IDM, AA decreased the number of gap junctions compared with the controls. Incubation of trachealis strips in vitro for 30 min with PGE2 increased the number of gap junctions by about threefold along with an increase in the size of the gap junctions. Similar incubation with PGI2, however, increased the number of gap junctions by approximately 60% without any change in the size. In the course of some control experiments, an interaction between carbachol and alcohol was observed such that alcohol caused an IDM-sensitive relaxation of carbachol-induced contractions, which was not observed when serotonin was the contractile agent. These results strongly suggest that PGE2 and PGI2 increase the formation of gap junctions in canine trachealis and that these prostanoids are released by 4-AP treatment. Leukotrienes may also be inhibitory in the formation of gap junctions, but FPL 55712 did not affect either the increase or the decrease in gap junctions after 4-AP.

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