Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation.
Blood Platelets
/ cytology
CD40 Ligand
/ blood
Chemokine CXCL12
/ pharmacology
Collagen
/ pharmacology
Healthy Volunteers
Heat-Shock Proteins
/ blood
Humans
Molecular Chaperones
/ blood
Platelet Activation
/ drug effects
Platelet-Derived Growth Factor
/ metabolism
p38 Mitogen-Activated Protein Kinases
/ blood
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
27
12
2019
accepted:
08
10
2020
entrez:
29
10
2020
pubmed:
30
10
2020
medline:
19
12
2020
Statut:
epublish
Résumé
CXCL12, also known as stromal cell-derived factor-1, is a chemokine classified into CXC families, which exerts its function by binding to specific receptors called CXCR4 and CXCR7. Human platelets express CXCR4 and CXCR7 on the plasma membrane. It has been reported that CXCL12 potentiates to induce platelet aggregation in cooperation with agonists including collagen. However, the precise roles and mechanisms of CXCL12 in human platelet activation are not fully elucidated. In the present study, we investigated the effect of simultaneous stimulation with low doses of collagen and CXCL12 on the activation of human platelets. The simultaneous stimulation with collagen and CXCL12 induced the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble CD40 ligand (sCD40L) from human platelets in addition to their aggregation, despite the fact that the simultaneous stimulation with thrombin receptor-activating peptide (TRAP) or adenosine diphosphate (ADP), and CXCL12 had little effects on the platelet aggregation. The agonist of Glycoprotein (GP) Ⅵ convulxin and CXCL12 also induced platelet aggregation synergistically. The monoclonal antibody against CXCR4 but not CXCR7 suppressed the platelet aggregation induced by simultaneous stimulation with collagen and CXCL12. The phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not p44/p42 MAPK, was induced by the simultaneous stimulation. In addition, the simultaneous stimulation with collagen and CXCL12 induced the phosphorylation of HSP27 and the subsequent release of phosphorylated-HSP27 from human platelets. SB203580, a specific inhibitor of p38 MAPK, attenuated the platelet aggregation, the phosphorylation of p38 MAPK and HSP27, the PDGF-AB secretion, the sCD40L release and the phosphorylated-HSP27 release induced by the simultaneous stimulation with collagen and CXCL12. These results strongly suggest that collagen and CXCL12 in low doses synergistically act to induce PDGF-AB secretion, sCD40L release and phosphorylated-HSP27 release from activated human platelets via p38 MAPK activation.
Identifiants
pubmed: 33119719
doi: 10.1371/journal.pone.0241139
pii: PONE-D-19-34102
pmc: PMC7595269
doi:
Substances chimiques
CXCL12 protein, human
0
Chemokine CXCL12
0
HSPB1 protein, human
0
Heat-Shock Proteins
0
Molecular Chaperones
0
Platelet-Derived Growth Factor
0
platelet-derived growth factor AB
0
CD40 Ligand
147205-72-9
Collagen
9007-34-5
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0241139Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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