Related Experiment Videos
Polymorphonuclear leukocyte apoptosis is inhibited by platelet-released mediators, role of TGFbeta-1
M Brunetti1, N Martelli, S Manarini
1Department of Oncology and Neuroscience, G. D'Annunzio University, Chieti, Italy. brunetti@cmns.mnegri.it
Abstract:
Platelets regulate several polymorphonuclear leukocyte (PMN) functions. We have found that thrombin-stimulated platelets potently inhibited PMN apoptosis. Cell-free supernatant from increasing concentrations of stimulated platelets inhibited PMN apoptosis in a dose-dependent manner, with an effect similar to that of corresponding concentrations of platelets. At the plateau, platelet supernatant inhibited PMN apoptosis by 54.6 +/- 6.8%, the anti-apoptotic activity being higher than that of GM-CSF and comparable to that of LPS. Neither IL-1ra nor a combination of anti-IL1alpha + betamAb affected the activity of platelet supernatant. In contrast a mAb recognizing the active form of TGF-beta1 significantly decreased this activity. Moreover, exogenous TGF-beta1 inhibited PMN apoptosis in a dose-dependent manner. The active form of this cytokine was indeed present in the supernatant of stimulated platelets at a concentration able to elicit an anti-apoptotic effect. The p38 MAPK inhibitor SB203580 prevented the anti-apoptotic effect of TGF-beta1 in a dose-dependent manner. Interestingly, it also prevented the anti-apoptotic effect of IL-1alpha, but not that of GM-CSF, LPS and dexamethasone. In conclusion, we report for the first time that PMN apoptosis is potently inhibited by platelet-released mediators, that TGF-beta1 mediates an important part of this effect, and that p38 MAPK is involved in the TGF-beta1 signaling leading to its anti-apoptotic effect. These results provide novel evidence to support the central role of platelets in inflammation.
Insights
Platelets release mediators that significantly inhibit polymorphonuclear leukocyte (PMN) apoptosis, with transforming growth factor-beta1 (TGF-β1) playing a key role. This platelet-induced anti-apoptotic effect involves the p38 mitogen-activated protein kinase (MAPK) pathway.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Platelets are known to regulate polymorphonuclear leukocyte (PMN) functions.
- The specific mechanisms by which platelets influence PMN apoptosis are not fully elucidated.
Purpose of the Study:
- To investigate the effect of thrombin-stimulated platelets on PMN apoptosis.
- To identify the key mediators and signaling pathways involved in platelet-mediated inhibition of PMN apoptosis.
Main Methods:
- Assessment of PMN apoptosis using cell-free supernatant from stimulated platelets at varying concentrations.
- Utilizing neutralizing antibodies against TGF-β1 and IL-1α.
- Employing the p38 MAPK inhibitor SB203580 to explore signaling pathways.
Main Results:
- Platelet supernatant potently inhibited PMN apoptosis in a dose-dependent manner.
- Transforming growth factor-beta1 (TGF-β1) was identified as a significant mediator of this anti-apoptotic effect.
- The p38 MAPK pathway was found to be involved in the TGF-β1-induced inhibition of PMN apoptosis.
Conclusions:
- Platelet-released mediators potently inhibit PMN apoptosis.
- TGF-β1 mediates a substantial portion of this platelet-driven anti-apoptotic effect.
- p38 MAPK signaling is crucial for the anti-apoptotic action of TGF-β1 in PMNs, highlighting platelets' role in inflammation.