Thromboxane and cysteinyl-leukotriene formation are differentially activated in spontaneously clotting whole human blood in vitro

Simmet, Thomas; Weide, Ingo

doi:10.1016/0049-3848(91)90146-n

Cited by 11 publications

(2 citation statements)

References 27 publications

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“…Hirudin is known to form stable complexes with thrombin by binding to the catalytic and anion bind ing sites of the thrombin molecule (Rydel et aI., 1990). Similar to findings in previous experiments with human blood cells (Simmet and Weide, 1991), we did not observe any effects of the thrombin in hibitors on the ionophore A23187-induced cystei nyl-L formation, thereby excluding a nonspecific interaction of those compounds with 5-lipoxygen ase activity.…”

Section: Discussionsupporting

confidence: 91%

Thrombin Stimulates Activation of the Cerebral 5-Lipoxygenase Pathway during Blood-Brain Cell Contact

Winking

Heldt

Simmet

1996

J Cereb Blood Flow Metab

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The purpose of this study was to identity the trigger mechanism activating the 5-lipoxygenase pathway during blood-brain cell contact and to estimate the contribution of blood and brain cells to the cysteinyl-leukotriene (LT) biosynthesis observed under these conditions. Incubation of dissociated rat brain cells in Krebs-Henseleit solution for up to 60 min did not stimulate any detectable cysteinyl-LT biosynthesis. Incubation of recalcified rat whole blood in vitro for up to 60 min led to release of only small amounts of cysteinyl-LT into the serum samples. However, coincubation of dissociated rat brain cells with physiologically recalcified autologous whole blood triggered a time-dependent release of large amounts of immunoreactive cysteinyl-LT into the serum samples. By reverse-phase HPLC, immunoreactive cysteinyl-LT was identified as a mixture of LTC4, LTD4, and LTE4. The extent of the 5-lipoxygenase stimulation depended on the amount of autologous blood coincubated with the dissociated brain cells. Activation of the 5-lipoxygenase pathway also occurred with coincubation of dissociated rat brain cells with recalcified autologous plasma. Stimulation of cysteinyl-LT biosynthesis during blood-brain cell contact remained unaffected by aprotinin, but concentration-dependent inhibition by the structurally and functionally unrelated thrombin inhibitors D-Phe-Pro-Arg-CH2Cl and recombinant hirudin was seen. Finally, when dissociated rat brain cells were incubated in Krebs-Henseleit solution in the presence of human alpha-thrombin, a concentration-dependent release of cysteinyl-LT into the buffer samples was observed. These data demonstrate that, in rats, during blood-brain cell contact, stimulation of the 5-lipoxygenase pathway in brain cells proceeds via alpha-thrombin as effector molecule.

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Section: Discussionsupporting

confidence: 91%

Thrombin Stimulates Activation of the Cerebral 5-Lipoxygenase Pathway during Blood-Brain Cell Contact

Winking

Heldt

Simmet

1996

J Cereb Blood Flow Metab

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“…Contact-mediated activation of the intrinsic coagulation cascade in human blood triggers the biosynthesis of cysteinyl-leukotrienes und leukotriene B 4 , which are generated via the 5-lipoxygenase pathway [110,111]. Thrombin generated by the coagulation cascade however, stimulates only the cyclooxygenase pathway and, thus, the synthesis of prostanoids, but had no effect on the 5-lipoxygenase pathway [112]. Unexpectedly, supplementation experiments with autologous cells showed that contact-mediated activation of the 5-lipoxygenase pathway in coagulated human whole blood takes place in monocytes, but not in neutrophils, suggesting a cell-specific activation mechanism [113].…”

Section: Plasmin-mediated Biosynthesis Of Lipid Mediators By Monocytesmentioning

confidence: 99%

Novel aspects and new roles for the serine protease plasmin

Syrovets

Simmet

2004

Cellular and Molecular Life Sciences (CMLS)

137

149

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The serine protease plasmin is distributed throughout the human body in the form of the zymogen plasminogen. The plasminogen activation system is mostly recognized for its fibrinolytic activity but is also upregulated in chronic inflammatory diseases, including atherosclerosis and arthritis. Plasmin can bind to a variety of cells, including monocytes, through low-affinity binding sites and triggers aggregation of neutrophils, platelet degranulation and arachidonate release from endothelial cells. In monocytes, plasmin elicits full-scale proinflammatory activation, including lipid mediator release, chemotaxis and cytokine expression, as well as induction of other proinflammatory genes. The effects of plasmin are specific, require the active catalytic center and can be antagonized by lysine analogues, implying binding of the plasmin molecule to the cell membrane through its lysine binding sites. In view of the upregulation of the fibrinolytic genes in chronic inflammatory diseases, cell activation by plasmin is likely to play a major pathophysiological role, a view that is further supported by data from transgenic mice.

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Harpagophytum procumbens: Wirkung von Extrakten auf die Eicosanoidbiosynthese in lonophor A23187-stimuliertem menschlichem Vollblut

Tippler

Syrovets

Loew³

et al. 1996

Phytopharmaka II

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Thromboxane and cysteinyl-leukotriene formation are differentially activated in spontaneously clotting whole human blood in vitro

Cited by 11 publications

References 27 publications

Thrombin Stimulates Activation of the Cerebral 5-Lipoxygenase Pathway during Blood-Brain Cell Contact

Thrombin Stimulates Activation of the Cerebral 5-Lipoxygenase Pathway during Blood-Brain Cell Contact

Novel aspects and new roles for the serine protease plasmin

Harpagophytum procumbens: Wirkung von Extrakten auf die Eicosanoidbiosynthese in lonophor A23187-stimuliertem menschlichem Vollblut

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