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Thromb Haemost 2000; 84(03): 478-483
DOI: 10.1055/s-0037-1614048
Commentary
Schattauer GmbH

Polymorphonuclear Leukocyte Apoptosis Is Inhibited by Platelet-released Mediators, Role of TGFβ-1

Mauro Brunetti
1   From the Department of Oncology and Neuroscience, “G. D’Annunzio” University, Chieti, Italy
2   Laboratory of Immunopathology, Chieti, Italy
,
Nicola Martelli
3   “G. Bizzozero” Laboratory of Blood and Vascular Cell Interactions, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
,
Stefano Manarini
3   “G. Bizzozero” Laboratory of Blood and Vascular Cell Interactions, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
,
Nicola Mascetra
1   From the Department of Oncology and Neuroscience, “G. D’Annunzio” University, Chieti, Italy
2   Laboratory of Immunopathology, Chieti, Italy
,
Piero Musiani
1   From the Department of Oncology and Neuroscience, “G. D’Annunzio” University, Chieti, Italy
2   Laboratory of Immunopathology, Chieti, Italy
,
Chiara Cerletti
3   “G. Bizzozero” Laboratory of Blood and Vascular Cell Interactions, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
,
Francesca B. Aiello
1   From the Department of Oncology and Neuroscience, “G. D’Annunzio” University, Chieti, Italy
2   Laboratory of Immunopathology, Chieti, Italy
,
Virgilio Evangelista
3   “G. Bizzozero” Laboratory of Blood and Vascular Cell Interactions, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
› Author AffiliationsThis work was supported in part by grants from Ministero dell’ Università e Ricerca Scientifica e Tecnologica (MURST 60%, 40%, and L623/96-D.M. 346 Ric/99) and the Italian National Research Council (Convenzione CNR-Consorzio Mario Negri Sud). The authors thank Drs. Giovanni de Gaetano, Silvano Sozzani, Franco O. Ranelletti and Andreina Poggi for critical reviewing of the manuscript.
Further Information

Publication History

Received 12 January 2000

Accepted after revision 03 April 2000

Publication Date:
14 December 2017 (online)

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Summary

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 dosedependent 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-IL1 α + β mAb affected the activity of platelet supernatant. In contrast a mAb recognizing the active form of TGF-β1 significantly decreased this activity. Moreover, exogenous TGF-β1 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-β1 in a dose-dependent manner. Interestingly, it also prevented the anti-apoptotic effect of IL-1α, 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-β1 mediates an important part of this effect, and that p38 MAPK is involved in the TGF-β1 signaling leading to its anti-apoptotic effect. These results provide novel evidence to support the central role of platelets in inflammation.

Key words

Platelets - neutrophils - apoptosis - inflammation - human
 

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