Increased CD40 ligand and platelet–monocyte aggregates in patients with type 1 diabetes mellitus

Harding, Scott; Sommerfield, A. J.; Sarma, Jaydeep; Twomey, Patrick J; Newby, David E.; Frier, Brian M.; Fox, Keith A.A.

doi:10.1016/j.atherosclerosis.2004.05.008

Cited by 98 publications

(79 citation statements)

References 28 publications

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“…Our previous studies (1,7,12), together with those of other investigators (2)(3)(4)(5)(6)(8)(9)(10)(11), highlighted the potential importance of platelet-monocyte complexes in inflammatory disease by demonstrating that activated platelets induce a proinflammatory phenotype characterized by the secretion of inflammatory mediators, including TNF-a, IL-8, and IL-1b (7)(8)(9)(10)(11). In this article, we report a specific mobilization of Ca 2+ and phosphorylation of Akt following coculture of monocytes with thrombin-activated platelets.…”

Section: Discussionmentioning

confidence: 84%

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Stephen

Emerson

Fox

et al. 2013

The Journal of Immunology

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Induction of an inflammatory monocyte phenotype by activated platelets is implicated in the pathogenesis of inflammatory diseases, including atherosclerosis. In this study, we investigated the early signaling events associated with this platelet-induced inflammatory phenotype. We report that coculture of human monocytes with activated platelets induces phosphorylation of Akt, together with rapid mobilization of intracellular Ca2+, and show that these signaling events can be uncoupled from monocyte binding to activated platelets. Specifically, Ab-inhibition studies and incubation of monocytes with activated platelet supernatant highlighted a role for secreted product(s) of activated platelets. We also identified a role for pertussis toxin–sensitive G protein–coupled receptors and excluded key candidates platelet-activating factor receptor and CCR5. Our results suggest that inhibition of monocyte–platelet interactions via PSGL-1 or P-selectin is not sufficient to prevent platelet-mediated monocyte activation in an inflammatory context. These findings have important implications for the development of therapeutics to treat diseases in which platelet–monocyte complexes are implicated in pathogenesis.

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Section: Discussionmentioning

confidence: 84%

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Stephen

Emerson

Fox

et al. 2013

The Journal of Immunology

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“…Platelets are critical mediators of hemostasis, coagulation, and wound healing and can form conjugates with CD8 + T cells or other leukocytes [14]. Increased frequencies of platelet/leukocyte complexes have been observed in the peripheral blood of HIV-infected ART recipients, as well as in the blood of patients with CVD, type I diabetes, or systemic lupus erythematosus [14][15][16][17], yet the biological significance of these interactions, or the cross-talk that occurs among these cell types, remains to be determined.…”

Section: Human Immunodeficiency Virus (Hiv) Infection Results In a Mamentioning

confidence: 99%

Inflammatory Function of CX3CR1⁺CD8⁺T Cells in Treated HIV Infection Is Modulated by Platelet Interactions

et al. 2016

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Increases in inflammation, coagulation, and CD8 + T-cell numbers are associated with an elevated cardiovascular disease (CVD) risk in human immunodeficiency virus (HIV)-infected antiretroviral therapy (ART) recipients. Circulating memory CD8 + T cells that express the vascular endothelium-homing receptor CX3CR1 (fractalkine receptor) are enriched in HIV-infected ART recipients. Thrombin-activated receptor (PAR-1) expression is increased in HIV-infected ART recipients and is particularly elevated on CX3CR1 + CD8 + T cells, suggesting that these cells could interact with coagulation elements. Indeed, thrombin directly enhanced T-cell receptor-mediated interferon γ production by purified CD8 + T cells but was attenuated by thrombin-induced release of transforming growth factor β by platelets. We have therefore identified a population of circulating memory CD8 + T cells in HIV infection that may home to endothelium, can be activated by clot-forming elements, and are susceptible to platelet-mediated regulation. Complex interactions between inflammatory elements and coagulation at endothelial surfaces may play an important role in CVD risk in HIV-infected ART recipients.

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“…It was, therefore, our objective to determine changes in circulating tissue factor plasma procoagulant activity (PCA) and other components of the blood coagulation system in healthy volunteers exposed to 24 h of hyperinsulinemia or hyperglycemia or combined hyperinsulinemia and hyperglycemia. In addition, we have examined their effect on platelet expression of CD40 ligand (CD40L), a proinflammatory member of the tumor necrosis superfamily (23)(24)(25), previously shown to be increased in diabetes (26,27).…”

mentioning

confidence: 99%

Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand

et al. 2006

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Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor. Diabetes 55: [202][203][204][205][206][207][208] 2006

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Increased CD40 ligand and platelet–monocyte aggregates in patients with type 1 diabetes mellitus

Cited by 98 publications

References 28 publications

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Inflammatory Function of CX3CR1⁺CD8⁺T Cells in Treated HIV Infection Is Modulated by Platelet Interactions

Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand

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Increased CD40 ligand and platelet–monocyte aggregates in patients with type 1 diabetes mellitus

Cited by 98 publications

References 28 publications

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Inflammatory Function of CX3CR1+CD8+T Cells in Treated HIV Infection Is Modulated by Platelet Interactions

Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand

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Inflammatory Function of CX3CR1⁺CD8⁺T Cells in Treated HIV Infection Is Modulated by Platelet Interactions