Galectin-1 and platelet factor 4 (CXCL4) induce complementary platelet responses in vitro

Dickhout, Annemiek; Tullemans, Bibian M. E.; Heemskerk, Johan W. M.; Thijssen, Victor L.; Kuijpers, Marijke J. E.; Koenen, Rory R.

doi:10.1371/journal.pone.0244736

Cited by 13 publications

(16 citation statements)

References 64 publications

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“…So far, this study has focussed on the effect of antiplatelet medications and combinations on the inflammatory properties of platelets. Interestingly, we have observed differential protein and extracellular vesicle secretion patterns after platelet activation throughout this, and in other studies [19,29,53,54]. In this study, we have observed differential CCL5 and CXCL4 release under the influence of different antiplatelet medications.…”

Section: Accepted Manuscriptsupporting

confidence: 76%

“…Interestingly, we have observed differential protein and extracellular vesicle secretion patterns after platelet activation throughout this, and in other studies. 19,29,53,54 In this study, we have observed differential CCL5 and CXCL4 release under the influence of different antiplatelet medications. This would suggest that these chemokines are differently packaged inside the α-granule of platelets and that their differential release is governed by autocrine feedback activation mechanisms.…”

Section: Discussionmentioning

confidence: 57%

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Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

Heinzmann

Coenen

Vajen

et al. 2021

TH Open

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The cause of atherothrombosis is rupture or erosion of atherosclerotic lesions, leading to an increased risk on myocardial infarction or stroke. Here, platelet activation plays a major role, leading to the release of bioactive molecules, e.g. chemokines and coagulation factors, and to platelet clot formation. Several antiplatelet therapies have been developed for secondary prevention of cardiovascular events, in which anticoagulant drugs are often combined. Besides playing a role in haemostasis, platelets are also involved in inflammation. However, it is unclear whether current antiplatelet therapies also affect platelet immune functions. In this study, the possible anti-inflammatory effects of antiplatelet medications on chemokine release were investigated using ELISA and on the chemotaxis of THP-1 cells towards platelet releasates. The cause of atherothrombosis is rupture or erosion of atherosclerotic lesions, leading to an increased risk on myocardial infarction or stroke. Here, platelet activation plays a major role, leading to the release of bioactive molecules, e.g. chemokines and coagulation factors, and to platelet clot formation. Several antiplatelet therapies have been developed for secondary prevention of cardiovascular events, in which anticoagulant drugs are often combined. Besides playing a role in haemostasis, platelets are also involved in inflammation. However, it is unclear whether current antiplatelet therapies also affect platelet immune functions. In this study, the possible anti-inflammatory effects of antiplatelet medications on chemokine release were investigated using ELISA and on the chemotaxis of THP-1 cells towards platelet releasates. We found that antiplatelet medication acetylsalicylic acid (ASA) led to reduced chemokine (C-C motif) ligand 5 (CCL5) and chemokine (C-X-C motif) ligand 4 (CXCL4) release from platelets, while leukocyte chemotaxis was not affected. Depending on the agonist, αIIbβ3- and P2Y12-inhibitors also affected CCL5 or CXCL4 release. The combination of ASA with a P2Y12 inhibitor or a phosphodiesterase inhibitor did not lead to an additive reduction on CCL5 or CXCL4 release. Interestingly, these combinations did reduce leukocyte chemotaxis. This study provides evidence that combined therapy of ASA and a P2Y12 or PDE3 inhibitor can decrease the inflammatory leukocyte recruiting potential of the releasate of activated platelets.

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Section: Accepted Manuscriptsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 57%

Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

Heinzmann

Coenen

Vajen

et al. 2021

TH Open

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“…Galectins are a family of b-galactoside-binding lectins that are involved in various physiologic processes and are established mediators of endocytosis of plasma membrane proteins and glycolipids [ 28 , 29 ]. Recent studies by us and others have shown an interplay between galectins and chemokines [ 30 , 31 ]. For example, there is an interplay between galectin-1 and CXCL4 in platelet activation [ 30 ], and CCL5 was shown to undergo physical interactions with galectin-3 [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies by us and others have shown an interplay between galectins and chemokines [ 30 , 31 ]. For example, there is an interplay between galectin-1 and CXCL4 in platelet activation [ 30 ], and CCL5 was shown to undergo physical interactions with galectin-3 [ 31 ]. However, whether galectins play a role in the uptake of CCL5 and CXCL4 remains a subject for future investigations.…”

Section: Discussionmentioning

confidence: 99%

“…Cell lysates were centrifuged for 5 min at 16.000× g and stored at −20 °C for ELISA. Sandwich ELISA was performed using human CCL5/RANTES (DY278) or human CXCL4/PF4 (DY795) DuoSet ELISA protocols (R&D Systems), respectively, as described [ 30 , 48 ]. Both ELISAs were found to detect neither CCL5 nor CXCL4 in samples of fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

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Rapid Internalization and Nuclear Translocation of CCL5 and CXCL4 in Endothelial Cells

Dickhout

Kaczor

Heinzmann

et al. 2021

IJMS

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The chemokines CCL5 and CXCL4 are deposited by platelets onto endothelial cells, inducing monocyte arrest. Here, the fate of CCL5 and CXCL4 after endothelial deposition was investigated. Human umbilical vein endothelial cells (HUVECs) and EA.hy926 cells were incubated with CCL5 or CXCL4 for up to 120 min, and chemokine uptake was analyzed by microscopy and by ELISA. Intracellular calcium signaling was visualized upon chemokine treatment, and monocyte arrest was evaluated under laminar flow. Whereas CXCL4 remained partly on the cell surface, all of the CCL5 was internalized into endothelial cells. Endocytosis of CCL5 and CXCL4 was shown as a rapid and active process that primarily depended on dynamin, clathrin, and G protein-coupled receptors (GPCRs), but not on surface proteoglycans. Intracellular calcium signals were increased after chemokine treatment. Confocal microscopy and ELISA measurements in cell organelle fractions indicated that both chemokines accumulated in the nucleus. Internalization did not affect leukocyte arrest, as pretreatment of chemokines and subsequent washing did not alter monocyte adhesion to endothelial cells. Endothelial cells rapidly and actively internalize CCL5 and CXCL4 by clathrin and dynamin-dependent endocytosis, where the chemokines appear to be directed to the nucleus. These findings expand our knowledge of how chemokines attract leukocytes to sites of inflammation.

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Galectin-1, a novel promising target for outcome prediction and treatment in SCLC

Corral

Puerto‐Nevado²,

Cedeño³

et al. 2022

Biomedicine & Pharmacotherapy

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Galectin-1 and platelet factor 4 (CXCL4) induce complementary platelet responses in vitro

Cited by 13 publications

References 64 publications

Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

Rapid Internalization and Nuclear Translocation of CCL5 and CXCL4 in Endothelial Cells

Galectin-1, a novel promising target for outcome prediction and treatment in SCLC

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