Related Experiment Video
Updated: Feb 8, 2026
Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration
James M Fox1,2, Fahima Kausar1, Amy Day1
1Receptor Biology Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
Insights
Activated platelets release chemokines like CXCL4, crucial for atherosclerosis. This study identifies chemokine receptor 1 (CCR1) as the primary receptor mediating CXCL4-induced monocyte migration, uncovering a key mechanism in inflammatory processes.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Activated platelets release CXCL4 (Platelet Factor-4), a chemokine implicated in atherosclerosis by promoting monocyte recruitment.
- The specific receptor mediating CXCL4's interaction with monocytes and its role in monocyte recruitment remain largely unidentified.
Purpose of the Study:
- To identify the receptor responsible for CXCL4-induced monocyte migration.
- To elucidate the signaling pathways involved in CXCL4-mediated monocyte chemotaxis.
Main Methods:
- Utilized THP-1 monocytic cell line and primary human monocytes.
- Assessed cell migration and intracellular calcium flux in response to CXCL4.
- Investigated the role of G protein-coupled receptors (GPCRs) and glycosaminoglycans.
- Tested the involvement of CXCR3 and CC-class chemokine receptors (CCRs), specifically CCR1.
Main Results:
- CXCL4 induced pertussis toxin-sensitive migration and calcium responses in THP-1 cells, indicating GPCR involvement.
- Chondroitinase ABC treatment abolished CXCL4-induced migration, suggesting a requirement for cell surface glycosaminoglycans.
- THP-1 cells were unresponsive to CXCR3 ligands, and a CXCR3 antagonist did not inhibit CXCL4-induced migration.
- CXCL4 induced migration and CCR1 endocytosis in CCR1-expressing cells and primary human monocytes.
- Monocyte chemotaxis induced by CXCL4 was sensitive to a CCR1 antagonist.
Conclusions:
- Chemokine receptor 1 (CCR1) is identified as the previously elusive receptor for CXCL4 on monocytes.
- CXCL4 binding to CCR1 mediates monocyte chemotaxis and endocytosis.
- CCR1 plays a significant role in inflammatory responses involving CXCL4, such as in atherosclerosis.
Abstract:
Activated platelets release micromolar concentrations of the chemokine CXCL4/Platelet Factor-4. Deposition of CXCL4 onto the vascular endothelium is involved in atherosclerosis, facilitating monocyte arrest and recruitment by an as yet, unidentified receptor. Here, we demonstrate that CXCL4 drives chemotaxis of the monocytic cell line THP-1. Migration and intracellular calcium responses induced by CXCL4 were pertussis toxin-sensitive, implicating a GPCR in signal transduction. Cell treatment with chondroitinase ABC ablated migration, suggesting that cis presentation of CXCL4 by cell surface glycosaminoglycans to a GPCR is required. Although CXCR3 has been previously described as a CXCL4 receptor, THP-1 cells were unresponsive to CXCR3 ligands and CXCL4-induced migration was insensitive to a CXCR3 antagonist, suggesting that an alternative receptor is involved. Interrogating CC-class chemokine receptor transfectants, we unexpectedly found that CXCL4 could induce the migration of CCR1-expressing cells and also induce CCR1 endocytosis. Extending our findings to primary human monocytes, we observed that CXCL4 induced CCR1 endocytosis and could induce monocyte chemotaxis in a CCR1 antagonist-sensitive manner. Collectively, our data identify CCR1 as a previously elusive monocyte CXCL4 receptor and suggest that CCR1 may play a role in inflammation where the release of CXCL4 is implicated.
More Related Videos
05:49Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
04:50Author Spotlight: Biological Standardization to Ensure Reproducibility and Harmonization in Research
Published on: August 4, 2023
Related Concept Videos
01:37Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
02:16Transcription Factors
01:30Adrenergic Agonists: Therapeutic Uses
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
02:15M-Cdk Drives Transition Into Mitosis
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
00:53Migration