Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps

Jansen, Marcel. P. B.; Emal, Diba; Teske, Gwendoline J. D.; Dessing, Mark C.; Florquin, Sandrine; Roelofs, Joris J. T. H.

doi:10.1016/j.kint.2016.08.006

Cited by 125 publications

(106 citation statements)

References 45 publications

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“…Platelets in supportive measures used in ARDS. Platelets contribute to comorbid conditions that frequently affect patients with ARDS, regardless of the frequency of the underlying cause (reviewed in [16,162]). In addition, inappropriate measures of systemic or respiratory support, including ventilation with excessive VT and high concentrations of inspired oxygen, are potential causes of morbidity and mortality in patients with ARDS (62,163).…”

Section: Translational Reviewmentioning

confidence: 99%

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Middleton

Rondina

Schwertz

et al. 2018

Am J Respir Cell Mol Biol

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Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.

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Section: Translational Reviewmentioning

confidence: 99%

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Middleton

Rondina

Schwertz

et al. 2018

Am J Respir Cell Mol Biol

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“…Several studies have suggested platelet activation exacerbates renal injury [10-11]. Our previous study [35] also showed that in rat renal ischemia-reperfusion injury, P-selectin was widely expressed in renal tissue, especially in renal tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 94%

“…Platelets play an important role in the processes of coagulation and inflammatory, and it has been shown that platelet activation exacerbates renal injury [10]. Recently, Jansen and colleagues found during renal ischemia reperfusion injury, necrotic cell-derived DNA led to platelet activation, platelet-granulocyte interaction, and subsequent neutrophil extracellular trap formation, leading to renal inflammation and further increase in tissue injury [11]. P-selectin (CD62P) is an adhesion molecule expressed on the activated endothelium and platelets, involves in the initial attachment of leukocytes to inflamed vascular endothelium [12].…”

Section: Introductionmentioning

confidence: 99%

Combination of Mean Platelet Volume/Platelet Count Ratio and the APACHE II Score Better Predicts the Short-Term Outcome in Patients with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy

Sheng

et al. 2018

Kidney Blood Press Res

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Background/Aims: Both the Acute physiology and Chronic Health Evaluation (APACHE II) score and mean platelet volume/platelet count Ratio (MPR) can independently predict adverse outcomes in critically ill patients. This study was aimed to investigate whether the combination of them could have a better performance in predicting prognosis of patients with acute kidney injury (AKI) who received continuous renal replacement therapy (CRRT). Methods: Two hundred twenty-three patients with AKI who underwent CRRT between January 2009 and December 2014 in a Chinese university hospital were enrolled. They were divided into survivals group and non-survivals group based on the situation at discharge. Receiver Operating Characteristic (ROC) curve was used for MPR and APACHE II score, and to determine the optimal cut-off value of MPR for in-hospital mortality. Factors associated with mortality were identified by univariate and multivariate logistic regression analysis. Results: The mean age of the patients was 61.4 years, and the overall in-hospital mortality was 48.4%. Acute cardiorenal syndrome (ACRS) was the most common cause of AKI. The optimal cut-off value of MPR for mortality was 0.099 with an area under the ROC curve (AUC) of 0.636. The AUC increased to 0.851 with the addition of the APACHE II score. The mortality of patients with of MPR > 0.099 was 56.4%, which was significantly higher than that of the control group with of ≤ 0.099 (39.6%, P= 0.012). Logistic regression analysis showed that average number of organ failure (OR = 2.372), APACHE II score (OR = 1.187), age (OR = 1.028) and vasopressors administration (OR = 38.130) were significantly associated with poor prognosis. Conclusion: Severity of illness was significantly associated with prognosis of patients with AKI. The combination of MPR and APACHE II score may be helpful in predicting the short-term outcome of AKI.

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“…The degree of tubular damage was assessed on PAS-D-stained 4-µm-thick sections by scoring tubular cell necrosis in 10 non-overlapping high-power fields (magnification 40x) in the corticomedullary junction. The degree of injury was scored by a pathologist in a blinded fashion on a 5-point scale: 0=no damage, 1=10% of the corticomedullary junction injured, 2=10-25%, 3=25-50%, 4=50-75%, 5=more than 75%, as described previously(8, 16).…”

Section: Methodsmentioning

confidence: 99%

Dual role of protease activated receptor 4 in acute kidney injury: contributing to renal injury and inflammation, while maintaining the renal filtration barrier upon acute renal ischemia reperfusion injury

Jansen

Claessen

Larsen

et al. 2019

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19 Ischemia reperfusion (I/R) injury triggers the activation of coagulation and inflammation processes 20 involved in the pathophysiology of acute kidney injury (AKI). Coagulation proteases upregulated 21 upon renal I/R injury activate protease activated receptors (PARs), which form an important 22 molecular link between inflammation and coagulation. PAR4 is the major thrombin receptor on 23 mouse platelets, and the only PAR that is expressed on both human and murine platelets. In 24 addition, PAR4 is expressed on other cells including podocytes. We here sought to determine the 25 contribution of PAR4 in the host response to renal I/R injury. Hence, we subjected PAR4 knockout 26 and wild-type mice to renal I/R injury. PAR4 knockout mice exhibited an increased tolerance to 27 renal tubular necrosis and showed a decreased neutrophil influx in response to renal I/R, 28 independent from platelet PAR4. On the other hand, PAR4 deficiency resulted in albumin cast 29 formation in peritubular capillaries and showed a tendency towards albuminuria. Transmission 30 Electron Microscopy revealed an increase in podocyte foot process effacement. Our findings 31 suggest that PAR4 contributes to renal injury likely through facilitating neutrophil migration, 32 independent from platelet PAR4. In addition, PAR4 fulfils an important function in the 33 maintenance of podocyte integrity following renal I/R insult. Subsequently, loss of PAR4 results 34 in albuminuria. 35 36 37 38 3 39 Introduction40 Acute kidney injury (AKI) is a common and costly complication in hospitalized patients, and is 41 independently associated with increased risk of death(1). AKI severity is directly related to patient 42 outcome; even minor changes in serum creatinine predict prognosis in AKI patients after major 43 surgery.(2) Despite the progress in knowledge of the underlying pathophysiology, a recent 44 epidemiological study demonstrated that the incidence of AKI continues to grow.(3) AKI is often 45 triggered by ischemia reperfusion (I/R), which leads to a complex interplay between inflammatory 46 and coagulation processes and renal tissue remodelling(4, 5). More comprehensive understanding 47 of the mechanism underlying these processes is needed to devise strategies to control AKI or 48 accelerate renal recovery. Host-derived coagulation proteases, such as the serine proteases 49 thrombin and factor Xa have been implicated in renal I/R injury (5, 6). Serine proteases regulate 50 haemostasis as well as inflammation and tissue remodelling, thus linking the underlying processes 51 involved in the pathophysiology of AKI (7, 8). Serine proteases elicit cellular effects through 52 cleavage of Protease Activated Receptors (PARs). PARs are a family of seven transmembrane 53 spanning G-protein-coupled receptors that are broadly expressed on immune cells, platelets, and 54 also on renal cells.(9) Upon cleavage, a previously cryptic sequence becomes exposed and acts as 55 a receptor-activated tethered ligand(10), hereby initiating downstream signalling. The PAR fa...

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Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps

Cited by 125 publications

References 45 publications

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Combination of Mean Platelet Volume/Platelet Count Ratio and the APACHE II Score Better Predicts the Short-Term Outcome in Patients with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy

Dual role of protease activated receptor 4 in acute kidney injury: contributing to renal injury and inflammation, while maintaining the renal filtration barrier upon acute renal ischemia reperfusion injury

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