Platelet-derived high-mobility group box 1 promotes recruitment and suppresses apoptosis of monocytes

Vogel, Sebastian; Rath, Dominik; Mack, Andreas F.; Loughran, Patricia; Lotze, Michael T.; Neal, Matthew D.; Billiar, Timothy R.; Gawaz, Meinrad

doi:10.1016/j.bbrc.2016.07.078

Cited by 40 publications

(40 citation statements)

References 28 publications

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“…Even under SCD steady state conditions, circulating platelets are significantly activated in patients, and are further activated in vaso-occlusive crisis and acute clinical events, such as acute chest syndrome (Westwick et al, 1983;Wun et al, 1997;Villagra et al, 2007;Garrido et al, 2017). Beyond their role in haemostasis, platelets provide a link between thrombosis and inflammation (Semple et al, 2011;Rondina et al, 2013;Morrell et al, 2014;Vogel et al, 2015aVogel et al, , 2016Murthy et al, 2017). More than two decades ago, Brittain et al (1993) proposed that activation of platelets has a contributory role in sickle vaso-occlusions.…”

Section: Platelets In Sickle Cell Diseasementioning

confidence: 99%

“…HMGB1 and TLR4 are key players in promoting inflammation in SCD (Xu et al, 2014). Targeted ablation of HMGB1 and TLR4 in circulating platelets in transgenic mice promoted anti-thrombotic and antiinflammatory effects (Vogel et al, 2015a(Vogel et al, , 2016. The HMGB1 inhibitor Glycyrrhizin (Mollica et al, 2007), a triterpene glycoside extracted from liquorice root, exerted potent inhibitory effects on platelet HMGB1 signalling (Vogel et al, 2014(Vogel et al, , 2015a.…”

Section: Targeting Hmgb1 and Nlrp3 Signalling In Plateletsmentioning

confidence: 99%

“…HMGB1 plasma levels are elevated in SCD patients at baseline and further increased during acute sickling events (Xu et al , ). HMGB1 induces thrombosis and inflammation when exported to the cell surface or released into the extracellular space by stressed or dying cells and activated platelets (Rouhiainen et al , ; Andersson & Tracey, ; Maugeri et al , ; Gawaz & Vogel, ; Vogel et al , , ,b, ). The effects of HMGB1 upregulation in the context of haemolysis are poorly understood.…”

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confidence: 99%

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Platelets at the crossroads of thrombosis, inflammation and haemolysis

Vogel

Thein

2018

Br J Haematol

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Platelets play a critical role at the interphase of thrombosis and inflammation, key features in haemolysis-associated disorders. Exercising this role requires expression of pattern recognition receptors by platelets, including toll-like receptor 4 (TLR4) and nucleotide-binding domain leucine rich repeat containing protein 3 (NLRP3), the latter forming intraplatelet multiprotein inflammasome complexes. Platelets are a potential target of various damage-associated molecular pattern (DAMP) molecules, such as free haem, a degradation by-product of haemoglobin oxidation during haemolysis, and high-mobility group box 1 (HMGB1), a DNA-binding protein released by dying or stressed cells and activated platelets. We have recently identified platelet TLR4, NLRP3, and Bruton tyrosine kinase (BTK) as critical regulators of platelet aggregation and thrombus formation, suggesting that the BTK inhibitor ibrutinib is a potential therapeutic target. Increasing evidence suggests that these and other DAMP-driven signalling mechanisms employed by platelets might be key in mediating inflammation and thrombosis encountered in haemolytic disorders. However, the precise regulatory triggers and their clinical relevance are poorly understood. We provide new insights into these less-well characterised platelet mechanisms, which are potentially targetable in haemolytic disorders.

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Section: Platelets In Sickle Cell Diseasementioning

confidence: 99%

Section: Targeting Hmgb1 and Nlrp3 Signalling In Plateletsmentioning

confidence: 99%

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Platelets at the crossroads of thrombosis, inflammation and haemolysis

Vogel

Thein

2018

Br J Haematol

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“…Platelet-derived HMGB1 has been shown to promote the recruitment of monocytes, and lead to inflammation and thrombosis [13]. Disulfide (or isomerized) HMGB1, characterized by 2 cysteine residues that are oxidized to form an S-S bond between C23 and C45, was found to induce NF-κB translocation and the secretion of inflammatory factors via TLR-4 in activated immune cells, while mutations of C23 or C45 abrogated the cytokine activity of HMGB1 [14].…”

Section: The Role Of Hmgb1 As a Redox Regulatormentioning

confidence: 99%

Sterile Inflammatory Role of High Mobility Group Box 1 Protein: Biological Functions and Involvement in Disease

et al. 2018

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High mobility group box 1 protein (HMGB1), a sterile inflammatory molecule and damage-associated molecular pattern (DAMP) released from various cells during stress has been implicated in inflammation. Several reports show that there is a direct relationship between inflammation and cardiovascular diseases (CVDs) such as thrombosis, hypertension, insulin resistance, preeclampsia, etc. Here, we intend to summarize the concept of the emerging link between HMGB1 and CVDs. Furthermore, we will discuss the possible therapeutic strategies that target HMGB1 for the treatment of different CVDs.

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“…Studies addressing the role of HMGB1 in myocardial infarction (MI) have generated conflicting results thus far, as detrimental [3-5] as well as salutary effects of HMGB1 [6-8] have been reported. Platelets store and, upon activation, export HMGB1 to the cell surface and release HMGB1 in significant amounts [9-11]. In a trauma/hemorrhagic shock model in mice with platelet-specific ablation of HMGB1, we have recently shown that platelet-derived HMGB1 is a critical mediator of thrombosis [9].…”

Section: Introductionmentioning

confidence: 99%

HMGB1 Expression Level in Circulating Platelets is not Significantly Associated with Outcomes in Symptomatic Coronary Artery Disease

Rath

Geisler

Gawaz

et al. 2017

Cell Physiol Biochem

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Background/Aims: Platelets express high-mobility group box 1 (HMGB1), a damage-associated molecular pattern molecule (DAMP) that triggers thrombosis and inflammation when present in extracellular space. The role of platelet-derived HMGB1 in coronary artery disease (CAD) remains unexplored. Methods: In a cohort study, we measured the expression of HMGB1 on the surface of circulating platelets in 183 patients with symptomatic CAD (stable CAD: n=80, acute coronary syndrome, ACS: n=103) at the time of percutaneous coronary intervention. All patients were tracked for course of left ventricular ejection fraction (LVEF), all-cause death (ACD), and myocardial infarction (MI) for 360 days after study inclusion. Results: Platelet HMGB1 expression did not significantly differ between stable CAD, unstable CAD, non-ST segment elevation myocardial infarction (NSTEMI), and ST segment elevation myocardial infarction (STEMI). Moreover, platelet HMGB1 did not significantly correlate with LVEF, neither at baseline nor at 6 months follow-up of the MI subgroup, and did not exert any significant effect on outcome (composite of ACD and/or MI as well as single events ACD and MI). Cumulative event-free survival of patients was not significantly different between HMGB1 levels above the median and HMGB1 levels below or equal to the median. Conclusion: These findings suggest that HMGB1 expressed on the surface of circulating platelets in patients with symptomatic CAD may not serve as a prognostic biomarker for this disease state.

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Platelet-derived high-mobility group box 1 promotes recruitment and suppresses apoptosis of monocytes

Cited by 40 publications

References 28 publications

Platelets at the crossroads of thrombosis, inflammation and haemolysis

Platelets at the crossroads of thrombosis, inflammation and haemolysis

Sterile Inflammatory Role of High Mobility Group Box 1 Protein: Biological Functions and Involvement in Disease

HMGB1 Expression Level in Circulating Platelets is not Significantly Associated with Outcomes in Symptomatic Coronary Artery Disease

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