Microparticles and acute renal dysfunction in septic patients

Tökés-Füzesi, Margit; Woth, Gábor; Ernyey, Balázs; Vermes, I.; Mühl, Diána; Bogár, Lajos; Kovaćs, Gábor L.

doi:10.1016/j.jcrc.2012.05.006

Cited by 45 publications

(39 citation statements)

References 27 publications

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“…In experimental endotoxemia, inhibition of platelet function was found to reduce endothelial dysfunction and to ameliorate multiple organ failure including acute lung injury (26,56,62). Recently, a role for platelets in the development of renal failure has been proposed for septic patients (69). However, it is still unclear whether antiplatelet drugs such as clopidogrel improve renal function in response to endotoxemia.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of COX-1 attenuates the formation of thromboxane A₂and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Mederle

Meurer

Castrop

et al. 2015

American Journal of Physiology-Renal Physiology

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Thromboxane (Tx) A2 has been suggested to be involved in the development of sepsis-induced acute kidney injury (AKI). Therefore, we investigated the impact of cyclooxygenase (COX)-1 and COX-2 activity on lipopolysaccharide (LPS)-induced renal TxA2 formation, and on endotoxemia-induced AKI in mice. Injection of LPS (3 mg/kg ip) decreased glomerular filtration rate (GFR) and the amount of thrombocytes to ∼50% of basal values after 4 h. Plasma and renocortical tissue levels of TxB2 were increased ∼10- and 1.7-fold in response to LPS, respectively. The COX-1 inhibitor SC-560 attenuated the LPS-induced fall in GFR and in platelet count to ∼75% of basal levels. Furthermore, SC-560 abolished the increase in plasma and renocortical tissue levels of TxB2 in response to LPS. The COX-2 inhibitor SC-236 further enhanced the LPS-induced decrease in GFR to ∼40% of basal values. SC-236 did not alter thrombocyte levels nor the LPS-induced increase in plasma and renocortical tissue levels of TxB2. Pretreatment with clopidogrel inhibited the LPS-induced drop in thrombocyte count, but did not attenuate the LPS-induced decrease in GFR and the increase in plasma TxB2 levels. This study demonstrates that endotoxemia-induced TxA2 formation depends on the activity of COX-1. Our study further indicates that the COX-1 inhibitor SC-560 has a protective effect on the decrease in renal function in response to endotoxin. Therefore, our data support a role for TxA2 in the development of AKI in response to LPS.

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Section: Discussionmentioning

confidence: 99%

Inhibition of COX-1 attenuates the formation of thromboxane A₂and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Mederle

Meurer

Castrop

et al. 2015

American Journal of Physiology-Renal Physiology

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“…Monocytes stimulated with LPSdeficient Neisseria meningitides shed fewer MVs compared with those induced by the wild type and display reduced tissue factor activity (28). Increased numbers of MVs have been reported in severely septic patients with ABBREVIATIONS: CCM, cell culture medium; FTIR, Fourier-transform infrared; MV, microvesicle; PC, principal component; PCA, principal component analysis; PS, phosphatidylserine; RPMI, Roswell Park Memorial Institute renal dysfunction (29), meningococcal infection (30), and candida infection (31); thus, MVs facilitate the immune response during sepsis caused by different pathogens. Gram-positive bacteria are also reported to induce the release of MVs (32).…”

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confidence: 99%

Infrared spectroscopic characterization of monocytic microvesicles (microparticles) released upon lipopolysaccharide stimulation

et al. 2017

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Microvesicles (MVs) are involved in cell-cell interactions, including disease pathogenesis. Nondestructive Fourier-transform infrared (FTIR) spectra from MVs were assessed as a technique to provide new biochemical insights into a LPS-induced monocyte model of septic shock. FTIR spectroscopy provided a quick method to investigate relative differences in biomolecular content of different MV populations that was complementary to traditional semiquantitative omics approaches, with which it is difficult to provide information on relative changes between classes (proteins, lipids, nucleic acids, carbohydrates) or protein conformations. Time-dependent changes were detected in biomolecular contents of MVs and in the monocytes from which they were released. Differences in phosphatidylcholine and phosphatidylserine contents were observed in MVs released under stimulation, and higher relative concentrations of RNA and α-helical structured proteins were present in stimulated MVs compared with MVs from resting cells. FTIR spectra of stimulated monocytes displayed changes that were consistent with those observed in the corresponding MVs they released. LPS-stimulated monocytes had reduced concentrations of nucleic acids, α-helical structured proteins, and phosphatidylcholine compared with resting monocytes but had an increase in total lipids. FTIR spectra of MV biomolecular content will be important in shedding new light on the mechanisms of MVs and the different roles they play in physiology and disease pathogenesis.-Lee, J., Wen, B., Carter, E. A., Combes, V., Grau, G. E. R., Lay, P. A. Infrared spectroscopic characterization of monocytic microvesicles (microparticles) released upon lipopolysaccharide stimulation.

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“… 11 , 12 , 27 Elevated PDMP levels correlate with the severity of sepsis in clinical studies. 28 – 30 Furthermore, studies investigating the effect of intravenous PDMPs in rats found that they resulted in deranged clotting, acute respiratory distress syndrome (ARDS), and a hemodynamic syndrome typical of sepsis. 31 , 32 Our results and previous reports suggest that the elevation of PDMPs in sepsis patients with DIC originates platelet activation during the progression of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Examination of biomarker expressions in sepsis-related DIC patients

Shimizu¹,

Konishi²,

Nomura³

2018

IJGM

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BackgroundDisseminated avascular coagulation (DIC) is the main cause of death among patients with sepsis. In particular, low platelet count is predictive of poor outcome. However, the significance of platelet activation in patients with sepsis-related DIC is poorly understood. To determine the characteristics of platelet-related abnormality in patients with sepsis-related DIC, we assessed the expression levels of several biomarkers.MethodsPlasma levels of biomarkers, including cytokines, chemokines, soluble selectins, platelet-derived microparticles (PDMPs), soluble vascular adhesion molecule 1, and high mobility group box protein 1 were measured by enzyme-linked immunosorbent assay at baseline and after 4, 7, 14, and 21 days of DIC treatment.ResultsDifferences in platelet activation and in the elevation of activated platelet-related PDMPs and of soluble P-selectin were seen between patients suffering from sepsis and hematologic malignancy with DIC. In addition, the elevation of interleukin (IL)-6 and thrombopoietin (TPO) was significant in sepsis patients with DIC. Furthermore, IL-6 and TPO promoted platelet activation in vitro.ConclusionAssessment of PDMPs, sP-selectin, IL-6, and TPO may be beneficial in the primary prevention of multi-organ failure in sepsis patients with DIC.

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Microparticles and acute renal dysfunction in septic patients

Cited by 45 publications

References 27 publications

Inhibition of COX-1 attenuates the formation of thromboxane A₂and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Inhibition of COX-1 attenuates the formation of thromboxane A₂and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Infrared spectroscopic characterization of monocytic microvesicles (microparticles) released upon lipopolysaccharide stimulation

Examination of biomarker expressions in sepsis-related DIC patients

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Microparticles and acute renal dysfunction in septic patients

Cited by 45 publications

References 27 publications

Inhibition of COX-1 attenuates the formation of thromboxane A2and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Inhibition of COX-1 attenuates the formation of thromboxane A2and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Infrared spectroscopic characterization of monocytic microvesicles (microparticles) released upon lipopolysaccharide stimulation

Examination of biomarker expressions in sepsis-related DIC patients

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Inhibition of COX-1 attenuates the formation of thromboxane A₂and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Inhibition of COX-1 attenuates the formation of thromboxane A₂and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice