Cytokine Secretion from Human Monocytes Potentiated by P-Selectin-Mediated Cell Adhesion

Suzuki, Junsuke; Hamada, Eri; Shodai, Tomonori; Kamoshida, Go; Kudo, Sanae; Itoh, Saotomo; Koike, Junzo; Nagata, Kisaburo; Irimura, Tatsuro; Tsuji, Tsutomu

doi:10.1159/000339857

Cited by 46 publications

(40 citation statements)

References 54 publications

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“…32 Additionally, monocyte adhesion to platelets resulted in the release of cytokines, thereby further promoting an inflammatory phenotype. 33 Our present data, showing increased CD11b expression and L-selectin shedding on both monocytes and neutrophils after rolling over the FLIPRs, are in accordance with these studies. Furthermore, other studies have shown that platelets are able to induce a proinflammatory phenotype on monocytes and neutrophils on complex formation, resulting in increased adhesive properties toward endothelial cells.…”

Section: Discussionsupporting

confidence: 93%

FLow-Induced PRotrusions (FLIPRs)

Tersteeg

Heijnen

Eckly

et al. 2014

Circulation Research

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Rationale: Platelets are the most important cells in the primary prevention of blood loss after injury. In addition, platelets are at the interface between circulating leukocytes and the (sub)endothelium regulating inflammatory responses. Objective: Our aim was to study the dynamic process that leads to the formation of procoagulant and proinflammatory platelets under physiological flow. Methods and Results: In the present study, we describe the formation of extremely long, negatively charged membrane strands that emerge from platelets adhered under flow. These flow-induced protrusions (FLIPRs) are formed in vitro on different physiological substrates and are also detected in vivo in a mouse carotid injury model. FLIPRs are formed downstream the adherent and activated platelets and reach lengths of 250 μm. FLIPR formation is shear-dependent and requires cyclophilin D, calpain, and Rac1 activation. It is accompanied by a disassembly of the F-actin and microtubule organization. Monocytes and neutrophils roll over FLIPRs in a P-selectin/P-selectin glycoprotein ligand-1–dependent manner, retrieving fragments of FLIPRs as microparticles on their surface. Consequently, monocytes and neutrophils become activated, as demonstrated by increased CD11b expression and L-selectin shedding. Conclusions: The formation of long platelet membrane extensions, such as the ones presented in our flow model, may pave the way to generate an increased membrane surface for interaction with monocytes and neutrophils. Our study provides a mechanistic model for platelet membrane transfer and the generation of monocyte/neutrophil–microparticle complexes. We propose that the formation of FLIPRs in vivo contributes to the well-established proinflammatory function of platelets and platelet-derived microparticles.

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Section: Discussionsupporting

confidence: 93%

FLow-Induced PRotrusions (FLIPRs)

Tersteeg

Heijnen

Eckly

et al. 2014

Circulation Research

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“…CD62P-PSGL-1 binding as well as platelet release of CCL5 and tumour necrosis factor superfamily member 14 (TNFSF14) induce monocyte expression of monocyte chemotactic protein 1 (MCP-1), TNF-α, IL-1β, IL-6, IL-8, IL-12 and macrophage inflammatory protein 1β (MIP-1β) in vitro [56,60,61].…”

Section: Pro-inflammatory Cytokine Expressionmentioning

confidence: 99%

Platelet Interaction with Innate Immune Cells

Kral¹,

Schrottmaier²,

Salzmann³

et al. 2016

Transfus Med Hemother

215

182

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Platelets are key players in haemostasis and prevent excessive bleeding upon injury. In response to vessel damage, platelets adhere and get activated at sites of injury, leading to recruitment of further platelets and thrombus formation. As injury represents a risk for infection, platelets recruit and activate leukocytes via direct cell-cell contacts and indirectly via cytokines and platelet-derived microvesicles. Activated platelets directly interact with leukocytes via P-selectin (CD62P) interaction with P-selectin glycoprotein ligand 1 (PSGL-1). This initial binding is enhanced by interaction of various other receptors, depending on the leukocyte subtype, leading to mutual activation and local cytokine release (reviewed in [1]), which modulates immune responses.Upon activation platelets release a variety of α-granule-derived cytokines, chemokines and growth factors [2]. The mechanism of packaging inflammatory cargo into α-granules, however, is incompletely understood [3]. Cytokines can be packaged into granules during megakaryopoiesis [4] either via biosynthesis in the megakaryocyte (e.g. platelet factor 4/CXCL4) or via endocytosis from the microenvironment (e.g. albumin) in the bone marrow [3]. Despite lacking a nucleus, platelets can splice and de novo synthesise proteins from megakaryocyte-derived (pre)mRNA as shown for 6]. Via their open canalicular system platelets also take up factors from the circulation. Further platelets can fuse with microvesicles, which leads to intercellular exchanges of chemotactic receptors such as C-C chemokine receptor type 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) [7,8]. Platelet cytokine levels have been demonstrated to be elevated in cancer patients [9,10], indicating either an active uptake of these factors by platelets or disease-related changes in megakaryopoiesis. This suggests that underlying pathologies might influence not only platelet reactivity but also their potential to modulate immune responses. KeywordsPlatelets · Platelet-leukocyte aggregates · P-selectin · Inflammation · Infection · Cardiovascular disease SummaryBeyond their traditional role in haemostasis and thrombosis, platelets are increasingly recognised as immune modulatory cells. Activated platelets and platelet-derived microparticles can bind to leukocytes, which stimulates mutual activation and results in rapid, local release of platelet-derived cytokines. Thereby platelets modulate leukocyte effector functions and contribute to inflammatory and immune responses to injury or infection. Platelets enhance leukocyte extravasation, differentiation and cytokine release. Platelet-neutrophil interactions boost oxidative burst, neutrophil extracellular trap formation and phagocytosis and play an important role in host defence. Platelet interactions with monocytes propagate their differentiation into macrophages, modulate cytokine release and attenuate macrophage functions. Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that pla...

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“…THP-1 human monocytes and mouse WEHI-274.1 monocytes were obtained from ATCC and were grown in RPMI-1640 medium or DMEM, respectively, containing 10% FCS and 0.05 mM 2-ME, as instructed by the supplier. FIHM were isolated from peripheral blood of healthy donors using Ficoll hydraplaque [16], and monocytes were enriched and verified using flow cytometer, as described previously [17].…”

Section: Cell Culturementioning

confidence: 99%

Involvement of fibrinolytic regulators in adhesion of monocytes to vascular endothelial cells induced by glycated LDL and to aorta from diabetic mice

Zhao

Ren

Moghadasain

et al. 2014

Journal of Leukocyte Biology

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Diabetes mellitus accelerates the development of atherosclerotic cardiovascular diseases. Monocyte adhesion is an early cellular event of atherogenesis. Elevated levels of glyLDL were common in diabetic patients. Our previous studies indicated that HSF1 and p22-phox (a subunit of the NOX complex) were involved in glyLDL-induced up-regulation of PAI-1 in vascular EC. The present study demonstrated that glyLDL significantly increased the adhesion of monocytes to the surface of cultured human umbilical vein or PAEC. Transfection of siRNA for PAI-1, p22-phox, or HSF1 in EC prevented glyLDL-induced monocyte adhesion to EC. uPA siRNA increased monocyte adhesion to EC. Exogenous uPA reduced monocyte adhesion induced by glyLDL or uPA siRNA. Exogenous PAI-1 restored monocyte adhesion to EC inhibited by PAI-1 siRNA or uPA. GlyLDL-induced monocyte adhesion to EC was inhibited by treatment of EC with RAP, an antagonist for LRP, and enhanced by uPAR antibody. The adhesion of monocytes to aorta from leptin db/db diabetic mice was significantly greater than to that from control mice, which was associated with elevated contents of PAI-1, uPA, p22-phox, and HSF1 in hearts of db/db mice. The results suggest that oxidative stress and fibrinolytic regulators (PAI-1, uPA, and uPAR) are implicated in the modulation of glyLDL-induced monocyte adhesion to vascular endothelium, which may play a crucial role in vascular inflammation under diabetes-associated metabolic disorder.

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Cytokine Secretion from Human Monocytes Potentiated by P-Selectin-Mediated Cell Adhesion

Cited by 46 publications

References 54 publications

FLow-Induced PRotrusions (FLIPRs)

FLow-Induced PRotrusions (FLIPRs)

Platelet Interaction with Innate Immune Cells

Involvement of fibrinolytic regulators in adhesion of monocytes to vascular endothelial cells induced by glycated LDL and to aorta from diabetic mice

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