Evidence of an interaction between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis in human platelets.
BACKGROUND
TGF-β1, SDF-1 and its cognate receptors CXCR4 and CXCR7 are expressed on the surface of human platelets and their expression levels are differently regulated in symptomatic coronary artery disease (CAD). All these proteins and receptors influence outcome in patients with symptomatic CAD. There might be a crosstalk between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis. Interrelations in CAD, especially in the context of platelets, are poorly understood. Therefore, we aimed to provide clinical and experimental evidence of interactions between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis in human platelets.


RESULTS
Blood samples of the complete cohort (n=284) were analysed for platelet surface expression levels of TGF-β1, SDF-1, CXCR4 and CXCR7 by flow cytometry. For stimulation assays platelet rich plasma was treated with TGF-β1 or SDF-1 and then analysed by flow cytometry. Multiple regression analyses were run to show independent associations of TGF-β1 with SDF-1, CXCR4, CXCR7 and clinical cofactors. Both, CXCR4 and CXCR7 significantly predicted TGF-β1 (p<0.001 and p<0.001, respectively). After stimulation with SDF-1, surface expression of TGF-β1 increased significantly when compared to resting platelets [mean TGF-β1 MFI 19.01 vs. mean TGF-β1 MFI 14.01, p<0.001]. Upon receptor blocking with either anti-CXCR4 or anti-CXCR7 monoclonal antibodies the enhancing effect of SDF-1 on TGF-β1 surface expression was significantly blunted. Stimulation with TGF-β1 did not alter SDF-1, CXCR4 or CXCR7 expression significantly.


CONCLUSIONS
We provide first clinical and experimental data suggesting a cross-talk between TGF-β and the SDF-1/CXCR4/CXCR7 axis in platelets which does not involve transcriptional modulation as shown previously for other cellular systems.
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Dominik
D
Rath
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Madhumita
M
Chatterjee
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Annabell
A
Holtkamp
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Nina
N
Tekath
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Oliver
O
Borst
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Sebastian
S
Vogel
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Karin
K
Müller
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Meinrad
M
Gawaz
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany. Electronic address: tobias.geisler@med.uni-tuebingen.de.
Tobias
T
Geisler
D000368:Aged; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060066:Protein Interaction Maps; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D053773:Transforming Growth Factor beta1
CXCL12; CXCR4; CXCR7 protein, human; Platelets; TGFbeta1