SDF-1α is a novel autocrine activator of platelets operating through its receptor CXCR4
| Autor: | Alastair W. Poole, Matthew T. Harper, Tony G. Walsh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
CXCR4
CXC chemokine receptor type 4 Blood Platelets medicine.medical_specialty Receptors CXCR4 Platelet Aggregation Thromboxane Signalling Biology Article PRP platelet-rich plasma Paracrine signalling CXCR7 CXC chemokine receptor type 7 Thromboxane A2 Internal medicine medicine Cyclic AMP Animals Humans Platelet Platelet activation Calcium Signaling Horses Receptor Autocrine signalling Secretion GPCR G-protein-coupled receptor AR-C-66096 AR-C TxA2 thromboxane A2 Thrombosis Cell Biology Platelet Activation Chemokine CXCL12 Cell biology Stromal cell-derived factor-1α Adenosine Diphosphate Autocrine Communication Endocrinology SDF-1α stromal cell-derived factor-1α Collagen Dense granule PGE1 prostaglandin E1 Platelet factor 4 |
| Zdroj: | Cellular Signalling |
| ISSN: | 1873-3913 0898-6568 |
| Popis: | Platelets store and secrete the chemokine stromal cell-derived factor (SDF)-1α upon platelet activation, but the ability of platelet-derived SDF-1α to signal in an autocrine/paracrine manner mediating functional platelet responses relevant to thrombosis and haemostasis is unknown. We sought to explore the role of platelet-derived SDF-1α and its receptors, CXCR4 and CXCR7 in facilitating platelet activation and determine the mechanism facilitating SDF-1α-mediated regulation of platelet function. Using human washed platelets, CXCR4 inhibition, but not CXCR7 blockade significantly abrogated collagen-mediated platelet aggregation, dense granule secretion and thromboxane (Tx) A2 production. Time-dependent release of SDF-1α from collagen-activated platelets supports a functional role for SDF-1α in this regard. Using an in vitro whole blood perfusion assay, collagen-induced thrombus formation was substantially reduced with CXCR4 inhibition. In washed platelets, recombinant SDF-1α in the range of 20–100 ng/mL− 1 could significantly enhance platelet aggregation responses to a threshold concentration of collagen. These enhancements were completely dependent on CXCR4, but not CXCR7, which triggered TxA2 production and dense granule secretion. Rises in cAMP were significantly blunted by SDF-1α, which could also enhance collagen-mediated Ca(2 +) mobilisation, both of which were mediated by CXCR4. This potentiating effect of SDF-1α primarily required TxA2 signalling acting upstream of dense granule secretion, whereas blockade of ADP signalling could only partially attenuate SDF-1α-induced platelet activation. Therefore, this study supports a potentially novel autocrine/paracrine role for platelet-derived SDF-1α during thrombosis and haemostasis, through a predominantly TxA2-dependent and ADP-independent pathway. Highlights • Collagen-induced platelet aggregation, TxA2 production and dense granule secretion require CXCR4 signalling. • CXCR4 regulates platelet thrombus formation. • SDF-1α-induced changes in cAMP and Ca(2 +) signalling require CXCR4. • SDF-1α, via CXCR4, enhances platelet activation responses to collagen, primarily through a TxA2-dependent and ADP-independent pathway. |
| Databáze: | OpenAIRE |
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