Search results for "ACTIVATION"
showing 10 items of 2079 documents
TREM-1 ligand expression on platelets enhances neutrophil activation
2007
Abstract The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1–specific signals are required for the platelet-induced augmentation of polymorphonuclear leu…
Cortisol, Platelet Serotonin Content, and Platelet Activity in Patients With Major Depression and Type 2 Diabetes
2015
OBJECTIVE Hypothalamic-pituitary-adrenal system dysfunction, serotonergic system alterations, and enhanced platelet activity may contribute to the increased cardiac risk in depression. This exploratory study examined associations between cortisol parameters, platelet serotonin (5-HT) content, and platelet activity markers in patients with newly diagnosed major depression (MD) and/or Type 2 diabetes (T2DM) compared with healthy controls. METHODS We compared cortisol awakening response (CAR), diurnal decrease in salivary cortisol concentrations (slope), platelet 5-HT, and platelet markers (CD40, CD40 ligand [CD40L], soluble CD40L, CD62P, β-thromboglobulin, and platelet factor-4) in 22 T2DM pa…
PHOSPHODIESTERASE INHIBITORS PIROXIMONE AND ENOXIMONE INHIBIT PLATELET AGGREGATION IN VIVO AND IN VITRO
1997
The phosphodiesterase type III inhibitors piroximone (PIR) and enoximone (ENO) exert positive inotropic and vasodilating effects in patients with severe heart failure. PIR and ENO raise cyclic AMP levels in cardiac and vascular smooth muscle cells. Platelet activity is also regulated by intracellular levels of cyclic AMP. In this study we have investigated the effects of PIR and ENO on platelet activity in vivo and in vitro. PIR and ENO inhibited ADP induced platelet aggregation in a time- and concentration-dependent manner with IC50-values of 67 +/- 14 mumol/l and 129 +/- 6 mumol/l, respectively. Coincubation of PIR with the adenylate cyclase activator iloprost resulted in a synergistic po…
Platelet-endothelial interaction in tumor angiogenesis and microcirculation
2003
Activated platelets release angiogenic growth factors and have therefore been proposed to contribute to tumor angiogenesis within a potentially prothrombotic tumor microcirculation. The aim of the study was to investigate interactions of platelets with the angiogenic microvascular endothelium of highly vascularized solid tumors during growth and in response to endothelial stimulation in comparison with normal subcutaneous tissue. Experiments were performed in the dorsal skinfold chamber preparation of C57BL/6J mice bearing the Lewis lung carcinoma (LLC-1) or methylcholanthrene-induced fibrosarcoma (BFS-1). Fluorescently labeled rolling and adherent platelets, red blood cell velocity, and ve…
Activation of cGMP-dependent Protein Kinase Iβ Inhibits Interleukin 2 Release and Proliferation of T Cell Receptor-stimulated Human Peripheral T Cells
2000
Several major functions of type I cGMP-dependent protein kinase (cGK I) have been established in smooth muscle cells, platelets, endothelial cells, and cardiac myocytes. Here we demonstrate that cGK Ibeta is endogenously expressed in freshly purified human peripheral blood T lymphocytes and inhibits their proliferation and interleukin 2 release. Incubation of human T cells with the NO donor, sodium nitroprusside, or the membrane-permeant cGMP analogs PET-cGMP and 8-pCPT-cGMP, activated cGK I and produced (i) a distinct pattern of phosphorylation of vasodilator-stimulated phosphoprotein, (ii) stimulation of the mitogen-activated protein kinases ERK1/2 and p38 kinase, and, upon anti-CD3 stimu…
A peptide from the staphylococcal protein Efb binds P‐selectin and inhibits the interaction of platelets with leukocytes
2022
AimsP-selectin is a key surface adhesion molecule for the interaction of platelets with leukocytes. We have shown previously that the N-terminal domain of S. aureus extracellular fibrinogen-binding protein (Efb) binds to P-selectin and interferes with platelet-leukocyte aggregate formation. Here, we aimed to identify the minimal Efb motif required for binding platelets and to characterise its ability to interfering with the formation of platelet-leukocyte aggregates.Methods and ResultsUsing a library of synthetic peptides, we mapped the platelet-binding site to a continuous 20 amino acid stretch. The peptide Efb68-87 was able to bind to resting and, to a greater extent, thrombin-stimulated …
Phosphorylation of CalDAG-GEFI by protein kinase A prevents Rap1b activation.
2013
Summary Background Signaling via protein kinase A (PKA) and protein kinase G (PKG) is critical for maintaining platelets in the resting state. Both kinases down-regulate the activity of the small GTPase Rap1b, a critical signaling switch for integrin activation and platelet aggregation. However, the mechanism of Rap1b regulation by PKA and PKG is largely unknown. Objective To identify the PKA phosphorylation sites in calcium and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), the main GEF for Rap1b in platelets, and the effect of CalDAG-GEFI phosphorylation in Rap1b activation. Methods The phosphorylation sites in CalDAG-GEFI were identified by radio-active phos…
High-throughput elucidation of thrombus formation reveals sources of platelet function variability
2019
In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based on assessment of the inter-and intra-subject variability in parameters of microspot-based thrombus formation, we aimed to determine the platelet factors contributing to this variation. Blood samples from 94 genotyped healthy subjects were analyzed for conventional platelet phenotyping: i.e. hematologic parameters, platelet glycoprotein (GP) expression levels and activation markers (24 parameters). Furthermore, platelets were activated by ADP, CRP-XL or TRAP. Parallel samples were investigated for whole-blood thrombus formation (6 mi…
Flow Cytometric Analysis of Calcium Mobilization in Whole‐Blood Platelets
2003
Flow cytometry provides a convenient method to evaluate platelet activation by following the kinetics of intracellular free Ca2+, using sensitive fluorescent indicators that can be loaded into intact cells. Moreover, in the clinical setting, whole-blood techniques have obvious advantages to avoid artifactual platelet activation and allow the maintenance of near-physiological conditions. This unit describes a fast and sensitive flow cytometric procedure using the Ca2+-sensitive dye fluo-3 AM and the platelet-specific antibody CD41-PE to determine the kinetics of intracellular Ca2+ mobilization in whole-blood platelets with minimal manipulation of the samples. The technique may be applied to …
Deciphering of ADP-induced, phosphotyrosine-dependent signaling networks in human platelets by Src-homology 2 region (SH2)-profiling.
2012
Tyrosine phosphorylation plays a central role in signal transduction controlling many important biological processes. In platelets, the activity of several signaling proteins is controlled by tyrosine phosphorylation ensuring proper platelet activation and aggregation essential for regulation of the delicate balance between bleeding and hemostasis. Here, we applied Src-homology 2 region (SH2)-profiling for deciphering of the phosphotyrosine state of human platelets activated by adenosine diphosphate (ADP). Applying a panel of 31 SH2-domains, rapid and complex regulation of the phosphotyrosine state of platelets was observed after ADP stimulation. Specific inhibition of platelet P2Y receptor…