Higher platelet reactivity and platelet-monocyte complex formation in Gram-positive sepsis compared to Gram-negative sepsis

Tunjungputri, Rahajeng N.; Heijden, Wouter van de; Urbanus, Rolf T.; Groot, Philip G. de; Ven, André van der; Mast, Quirijn de

doi:10.1080/09537104.2016.1252837

Cited by 33 publications

(31 citation statements)

References 42 publications

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“…The plasma levels of fMLF were increased in these conditions, and also in high‐fat‐diet‐treated mice due to altered microbiome where it impaired the glucose tolerance and insulin secretion . Many of these infectious and inflammatory conditions are associated with a risk for thrombosis and other platelet‐mediated complications . The concentrations of fMLF in the intestinal milieu have been reported to be at least in micromolar ranges .…”

Section: Discussionmentioning

confidence: 99%

The formyl peptide fMLF primes platelet activation and augments thrombus formation

Salamah

Ravishankar

Vaiyapuri³

et al. 2019

Journal of Thrombosis and Haemostasis

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The role of formyl peptide receptor 1 (FPR1) and its ligand, fMLF, in the regulation of platelet function, hemostasis, and thrombosis is largely unknown. Fpr1‐deficient mice and selective inhibitors for FPR1 were used to investigate the function of fMLF and FPR1 in platelets. N‐formyl‐methionyl‐leucyl‐phenylalanine primes platelet activation and augments thrombus formation, mainly through FPR1 in platelets. Formyl peptide receptor 1 plays a pivotal role in the regulation of platelet function. Background Formyl peptide receptors (FPRs) play pivotal roles in the regulation of innate immunity and host defense. The FPRs include three family members: FPR1, FPR2/ALX, and FPR3. The activation of FPR1 by its high‐affinity ligand, N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLF) (a bacterial chemoattractant peptide), triggers intracellular signaling in immune cells such as neutrophils and exacerbates inflammatory responses to accelerate the clearance of microbial infection. Notably, fMLF has been demonstrated to induce intracellular calcium mobilization and chemotaxis in platelets that are known to play significant roles in the regulation of innate immunity and inflammatory responses. Despite a plethora of research focused on the roles of FPR1 and its ligands such as fMLF on the modulation of immune responses, their impact on the regulation of hemostasis and thrombosis remains unexplored. Objective To determine the effects of fMLF on the modulation of platelet reactivity, hemostasis, and thrombus formation. Methods Selective inhibitors for FPR1 and Fpr1‐deficient mice were used to determine the effects of fMLF and FPR1 on platelets using various platelet functional assays. Results N‐formyl‐methionyl‐leucyl‐phenylalanine primes platelet activation through inducing distinctive functions and enhances thrombus formation under arterial flow conditions. Moreover, FPR1 regulates normal platelet function as its deficiency in mouse or blockade in human platelets using a pharmacological inhibitor resulted in diminished agonist‐induced platelet activation. Conclusion Since FPR1 plays critical roles in numerous disease conditions, its influence on the modulation of platelet activation and thrombus formation may provide insights into the mechanisms that control platelet‐mediated complications under diverse pathological settings.

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Section: Discussionmentioning

confidence: 99%

The formyl peptide fMLF primes platelet activation and augments thrombus formation

Salamah

Ravishankar

Vaiyapuri³

et al. 2019

Journal of Thrombosis and Haemostasis

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“…The interactions are intermediate in adult SIRS and predominantly pro-stimulatory in adult sepsis. SELP (p-selectin) has been implicated in sepsis for some considerable time and may contribute to neutrophil recruitment and NET formation (247)(248)(249)(250). Ascorbic acid treatment is in focus as a potential therapy directed toward these cellto-cell interactions (251,252).…”

Section: Myl9mentioning

confidence: 99%

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

et al. 2020

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Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS) of non-infectious origin. Sepsis presents with a range of pathophysiological and genetic features which make clinical differentiation from SIRS very challenging. This may reflect a poor understanding of the key gene inter-activities and/or pathway associations underlying these disease processes. Improved understanding is critical for early differential recognition of sepsis and SIRS and to improve patient management and clinical outcomes. Judicious selection of gene biomarkers suitable for development of diagnostic tests/testing could make differentiation of sepsis and SIRS feasible. Here we describe a methodologic framework for the identification and validation of biomarkers in SIRS, sepsis and septic shock patients, using a 2-tier gene screening, artificial neural network (ANN) data mining technique, using previously published gene expression datasets. Eight key hub markers have been identified which may delineate distinct, core disease processes and which show potential for informing underlying immunological and pathological processes and thus patient stratification and treatment. These do not show sufficient fold change differences between the different disease states to be useful as primary diagnostic biomarkers, but are instrumental in identifying candidate pathways and other associated biomarkers for further exploration.

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“…86 Especially infections with gram-positive cocci, such as Staphylococcus aureus or Streptococcus pneumoniae, are characterized by systemic platelet activation and platelet hyperreactivity, and this may contribute to the increased risk for thrombotic vascular complications. 87,88 Profound thrombocytopenia or bleeding complications are infrequently observed in patients with bacterial infections, unless there is progression to severe sepsis with disseminated intravascular coagulation. The zoonotic bacterial infection leptospirosis is an exception to this rule, as thrombocytopenia and hemorrhagic manifestations are relatively common.…”

Section: Leptospirosismentioning

confidence: 99%

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases

Putri

Tunjungputri

Groot

et al. 2018

Semin Thromb Hemost

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Thrombocytopenia is a well-known manifestation of acute tropical infectious diseases. The role of platelets in infections has received much attention recently because of their emerging activities in modulation of inflammatory responses, host defense, and vascular integrity. However, while many studies have addressed thrombocytopenia in tropical infections, abnormalities in platelet function have been largely overlooked. This is an important research gap, as platelet dysfunction may contribute to the bleeding tendency that characterizes some tropical infections. The development of novel platelet function assays that can be used in thrombocytopenic conditions (e.g., flow cytometry assays) has contributed to important new insights in recent years. In this review, the importance of platelets in tropical infections is discussed with special emphasis on the underlying mechanisms and consequences of thrombocytopenia and platelet dysfunction in these infections. Special attention is paid to malaria, a disease characterized by microvascular obstruction in which bleeding is rare, and to infections in which bleeding is common, such as dengue, other viral hemorrhagic fevers, and the bacterial infection leptospirosis. Given the importance of platelet function abnormalities in these infections, the development of affordable assays for monitoring of platelet function in low-resource countries, as well as pharmacologic interventions to prevent or reverse platelet function abnormalities, might improve clinical care and the prognosis of these infections.

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Higher platelet reactivity and platelet-monocyte complex formation in Gram-positive sepsis compared to Gram-negative sepsis

Cited by 33 publications

References 42 publications

The formyl peptide fMLF primes platelet activation and augments thrombus formation

The formyl peptide fMLF primes platelet activation and augments thrombus formation

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases

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