Cited by 317Platelet Disorders and TreatmentsChemokine receptors and signalingBlood Coagulation and Thrombosis Mechanisms

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Platelet chemokines and chemokine receptors, linking hemostasis, inflammation, and host defense

GEAR, ADRIAN R.L., CAMERINI, DAVID·2003·Microcirculation

DOI 10.1038/sj.mn.7800198

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Abstract

Blood platelets play critical roles in hemostasis, providing rapid essential protection against bleeding and catalyzing the important slower formation of stable blood clots via the coagulation cascade. They are also involved in protection from infection by phagocytosis of pathogens and by secreting chemokines that attract leukocytes. Platelet function usually is activated by primary agonists such as adenosine diphosphate (ADP), thrombin, and collagen, whereas secondary agonists like adrenalin do not induce aggregation on their own but become highly effective in the presence of low levels of primary agonists. Current research has revealed that chemokines represent an important additional class of agonists capable of causing significant activation of platelet function. Early work on platelet alpha-granule proteins suggested that platelet factor 4, now known as CXCL4, modulated aggregation and secretion induced by low agonist levels. Subsequent reports revealed the presence in platelets of messenger RNA for several additional chemokines and chemokine receptors. Three chemokines in particular, CXCL12 (SDF-1), CCL17 (TARC), and CCL22 (MDC), recently have been shown to be strong and rapid activators of platelet aggregation and adhesion after their binding to platelet CXCR4 or CCR4, when acting in combination with low levels of primary agonists. CXCL12 can be secreted by endothelial cells and is present in atherosclerotic plaques, whereas CCL17 and CCL22 are secreted by monocytes and macrophages. Platelet activation leads to the release of alpha-granule chemokines, including CCL3 (MIP-1alpha), CCL5 (RANTES), CCL7 (MCP-3), CCL17, CXCL1 (growth-regulated oncogene-alpha), CXCL5 (ENA-78), and CXCL8 (IL-8), which attract leukocytes and further activate other platelets. These findings help to provide a direct linkage between hemostasis, infection, and inflammation and the development of atherosclerosis.

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Authors: GEAR, A. R. L., & CAMERINI, D.
Affiliations: University of Virginia (US)
Corresponding author: GEAR, ADRIAN R.L.
ORCID: CAMERINI, DAVID
Venue: Microcirculation
Publisher: Wiley
Published: 2003-07
Volume: 10
Issue: 3-4
Pages: 335-350
ISSN: 1073-9688 (ISSN-L)
1549-8719
DOI: 10.1038/sj.mn.7800198
OpenAlex: W2001798594
Cited by: 317
References: 161
Citations by year: 2026: 4 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 7 · 2018: 10 · 2017: 13 · 2016: 17 · 2015: 28 · 2014: 18 · 2013: 6 · 2012: 21
FWCI: 2.80
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2401 d)
Locations: Microcirculation (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r29ai039943-01a1)
National Institute of Allergy and Infectious Diseases (AI 39943)
National Institute of Diabetes and Digestive and Kidney Diseases (DK59004)
Topics: Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords: chemokine receptors, platelet activation, platelet aggregation, hemostasis, inflammation, host defense, CXCL12, CCL17, CCL22, CXCR4, CCR4, alpha-granule proteins, atherosclerosis, leukocyte recruitment, platelet factor 4, CCL3, RANTES, CCL7, interleukin-8
MeSH terms: Blood Platelets, Hemostasis, Humans, Immunity, Inflammation, Chemokines, Receptors, Chemokine

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Platelet chemokines and chemokine receptors, linking hemostasis, inflammation, and host defense

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