Lipopolysaccharide‐stimulated Leukocytes Contribute to Platelet Aggregative Dysfunction, Which is Attenuated by Catalase in Rats

Dong, Huei-Ping; Chunag, I-Chun; Wang, Dean-Chuan; Huang, Li-Ju; Lee, Chu-I; Tsai, Jen-Hsiang; Yang, Rei‐Cheng

doi:10.1016/s1607-551x(10)70090-5

Cited by 6 publications

(7 citation statements)

References 30 publications

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“…In the present study, experimental endotoxemia, by means of a 4-hour infusion of 0.5 ng/kg/hour LPS, reduced primary hemostasis (platelet aggregation, reduced by Multiplate) and enhanced secondary hemostasis (clot formation) in whole blood (reduced R time (enhanced coagulation initiation) and increased G (enhanced clot strength) at 4 h by TEG) in accordance with previous findings [23]–[25], [27]–[29]. During endotoxemia, fibrinolysis was enhanced (increased breakdown of the platelet-fibrin clot, CLT reduced at 4 h by TEG), which probably explains the observed reduction in the functional fibrinogen level (reduced strength of the fibrin clot, MA reduced at 4 h by FF).…”

Section: Discussionsupporting

confidence: 93%

“…This has been documented by TEG/ROTEM and has been reproduced in studies using experimental human [23] and animal [25]–[27] models of endotoxemia [23], [25]–[27]. Also, platelet aggregation is profoundly reduced in septic patients [19]–[22] and decreases with disease severity [20]–[22], which has also been reproduced in experimental human [23], [24] and animal [28], [29] models of endotoxemia.…”

Section: Discussionmentioning

confidence: 85%

“…Multiple Platelet function Analyzer; Multiplate®, Verum Diagnostica GmbH, Munich, Germany) [8] reveal both fibrinolysis and platelet function. Several studies have characterized the coagulopathy in sepsis [9]–[22] and experimental human [23], [24] and animal [25]–[29] endotoxemia by these tests.…”

Section: Introductionmentioning

confidence: 99%

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Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers

et al. 2013

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BackgroundSepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG).MethodsProspective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations were applied.ResultsEndotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05), whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore, during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049). After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001).ConclusionsEndotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are critically involved in the vasculo-fibrinolytic response to acute inflammation is important given that disturbances in the vascular system contribute significantly to morbidity and mortality in critically ill patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 85%

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Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers

et al. 2013

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“…Studies have shown that O 2 - reduces the threshold for platelet activation to collagen [ 14 ]. In addition, Dong et al showed that catalase in vitro reduces the likelihood of platelet dysfunction during LPS-induced sepsis [ 41 ]. In the present study, using SOD and catalase, we demonstrated that reactive oxygen species, such as O 2 - and H 2 O 2 do indeed contribute to enhancement of platelet function followed acute exposure to LPS.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide potentiates platelet responses via toll-like receptor 4-stimulated Akt-Erk-PLA2 signalling

et al. 2017

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Lipopolysaccharide (LPS) from the cell envelope of Gram-negative bacteria is a principal cause of the symptoms of sepsis. LPS has been reported to modulate the function of platelets although the underlying mechanisms of LPS action in these cells remain unclear. Platelets express the Toll-like receptor 4 (TLR4) which serves as a receptor for LPS, although the potential role of TLR4 and associated cell signalling in controlling platelet responses to LPS has not been extensively explored. In this study, we therefore investigated the actions of LPS prepared from different strains of Escherichia coli on platelet function, the underlying signalling mechanisms, and the potential role of TLR4 in orchestrating these. We report that LPS increased the aggregation of washed platelets stimulated by thromboxane (U46619) or GPVI collagen receptor agonists, effects that were prevented by a TLR4 antagonist. Associated with this, LPS enhanced fibrinogen binding, P-selectin exposure and reactive oxygen species (ROS) release. Increase of ROS was found to be important for the actions of LPS on platelets, since these were inhibited in the presence of superoxide dismutase or catalase. The effects of LPS were associated with phosphorylation of Akt, ERK1/2 and PLA2 in stimulated platelets, and inhibitors of PI3-kinase, Akt and ERK1/2 reduced significantly LPS enhanced platelet function and associated ROS production. Furthermore, inhibition of platelet cyclooxygenase or the thromboxane receptor, revealed an important role for thromboxane A2. We therefore conclude that LPS increases human platelet activation through a TLR4-PI3K-Akt-ERK1/2-PLA2 -dependent pathway that is dependent on ROS and TXA2 formation.

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“…Platelet count was determined by an electronic counter (Sysmex Microcellcounter F-800; Toa Medical Electronics, Kobe, Japan). The platelet count in the PRP was adjusted to 400,000/μL by dilution with PPP as needed [5,6,7,8]. Platelet aggregation in PRP was induced by 2.5 μM ADP and measured with an aggregometer (PACKS-4 platelet aggregation chromogenic kinetic system; Helena Laboratories, Beaumont, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

The Effect of Butanolides from Cinnamomum tenuifolium on Platelet Aggregation

Dong

Chen

et al. 2013

Molecules

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This study investigated the effects of isotenuifolide and tenuifolide B from the stems of Cinnamomum tenuifolium on adenosine diphosphate (ADP)-induced human platelet aggregation. Treatment of human platelet-rich plasma with isotenuifolide (1 and 2 μg/μL) and tenuifolide B (1, 2 and 4 μg/μL) did not have any significant effect on human platelet aggregation in vitro, however, treatment of human platelet-rich plasma with isotenuifolide (4 μg/μL) resulted in an inhibitory effect on platelet aggregation, suggesting the potential of this compound as an anti-atherosclerogenic agent in humans. Isotenuifolide is a new butanolide compound, whose structure was characterized by spectral analyses.

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Lipopolysaccharide‐stimulated Leukocytes Contribute to Platelet Aggregative Dysfunction, Which is Attenuated by Catalase in Rats

Cited by 6 publications

References 30 publications

Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers

Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers

Lipopolysaccharide potentiates platelet responses via toll-like receptor 4-stimulated Akt-Erk-PLA2 signalling

The Effect of Butanolides from Cinnamomum tenuifolium on Platelet Aggregation

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