Activated platelets signal chemokine synthesis by human monocytes.

Weyrich, Andrew S.; Elstad, Mark R.; McEver, Rodger P.; McIntyre, Thomas M.; Moore, Kevin L.; Morrissey, James H.; Prescott, Stephen M.; Zimmerman, Guy A.

doi:10.1172/jci118575

Cited by 567 publications

(536 citation statements)

References 81 publications

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“…Leukocyte-derived microparticles trigger endothelial cells to produce interleukin-6 (39,40). P-selectin, which is present on platelet-derived microparticles, triggers monocytes to express not only tissue factor, but also chemokines (41,42). Platelet-derived microparticles transport arachidonic acid to endothelial cells and induce the expression of cyclooxygenase 2 and the increased production of prostacyclin (43), enhance the interaction between monocytes and endothelial cells (44), and enhance leukocyte aggregation and their accumulation on the endothelium (45).…”

Section: Discussionmentioning

confidence: 99%

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

Berckmans¹,

Nieuwland²,

Tak³

et al. 2002

Arthritis & Rheumatism

180

169

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Objective. To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.Methods. Microparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n ‫؍‬ 10) and patients with other forms of arthritis (non-RA; n ‫؍‬ 10) and in plasma from healthy subjects (n ‫؍‬ 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F 1؉2 (by enzyme-linked immunosorbent assay [ELISA]) and thrombin-antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo.Results. Plasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non-RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F 1؉2 (median 66 nM) and TAT complex (median 710 g/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 g/liter, respectively) as well as the controls (1.0 nM and 2.9 g/liter, respectively). Conclusion. Synovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII-dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.

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Section: Discussionmentioning

confidence: 99%

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

Berckmans¹,

Nieuwland²,

Tak³

et al. 2002

Arthritis & Rheumatism

180

169

View full text Add to dashboard Cite

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“…Notably, however, the main receptors facilitating PLAs (i.e. P-selectin, CD40L, GPIbα, GPVI, GPIIb/IIIa on platelets and PSGL-1, CD40, Mac-1 on leukocytes) are consistently involved in both mice and human (2,4,6,8,31–38). …”

Section: Translational Aspects Of Animal Modelsmentioning

confidence: 99%

“…Platelet-leukocyte interactions are further stabilised by crosstalk of numerous additional receptor/ligand pairs that were reviewed previously (1,5) and trigger mutual activation and release of granular content by both platelets and leukocytes, thereby modulating leukocyte function and fine-tuning immune responses (5). Importantly, platelet-leukocyte interactions facilitate leukocyte recruitment and extravasation to sites of inflammation (6,7), promote leukocyte release of pro-inflammatory mediators (8,9), oxidative burst, phagocytosis, release of neutrophil extracellular traps (NETs) (10,11), and may also dampen inflammation under some pathological conditions (12–14). …”

Section: Introductionmentioning

confidence: 99%

Measuring and interpreting platelet-leukocyte aggregates

et al. 2018

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Platelets, besides their specialised role in haemostasis and atherothrombosis, actively modulate innate and adaptive immune responses with crucial roles in immune surveillance, inflammation and host defence during infection. An important prerequisite for platelet-mediated changes of immune functions involves direct engagement with different types of leukocytes. Indeed, increased platelet-leukocyte aggregates (PLAs) within the circulation and/or locally at the site of inflammation represent markers of many thrombo-inflammatory diseases, such as cardiovascular diseases, acute lung injury, renal and cerebral inflammation. Therefore, measurement of PLAs could provide an attractive and easily accessible prognostic and/or diagnostic tool for many diseases. To measure PLAs in different (patho-)physiological settings in human and animal models flow cytometric and microscopic approaches have been applied. These techniques represent complementary tools to study different aspects relating to the involvement of leukocyte subtypes and molecules, as well as location of PLAs within tissues, dynamics of their interactions and/or dynamic changes in leukocyte and platelet behaviour. This review summarises various approaches to measure and interpret PLAs and discusses potential experimental factors influencing platelet binding to leukocytes. Furthermore, we summarise insights gained from studies regarding the underlying mechanism of platelet-leukocyte interactions and discuss implications of these interactions in health and disease.

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“…In parallel, endothelial PAF has been implicated in juxtacrine stimulation of integrin function in PMN tethered through P-selectin on thrombin-stimulated endothelium (54). Although P-selectin itself does not trigger arrest of PMN under flow, it may cooperate with chemoattractants to stimulate leukocytes (55). It has recently been confirmed that PMN adhesion on immobilized platelets under shear flow requires both a juxtacrine activation mechanism involving PAF and an enhancing signal from P-selectin (56).…”

Section: Involvement Of Platelet-activating Factor (Paf) and Leukotrimentioning

confidence: 99%

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

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The integrin heterodimer CD11b/CD18 (␣M␤2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2␣ (8-epi-PGF2␣) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear-resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet ␣IIb␤3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac-1-mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro, indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs.

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Activated platelets signal chemokine synthesis by human monocytes.

Cited by 567 publications

References 81 publications

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

Measuring and interpreting platelet-leukocyte aggregates

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

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