Polymorphonuclear leukocyte apoptosis is inhibited by platelet-released mediators, role of TGFβ-1

M. Brunetti, N. Martelli, S. Manarini, N. Mascetra, P. Musiani, C. Cerletti, F. B. Aiello, V. Evangelista

Research output: Contribution to journalArticle

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-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 potentily 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 result provide novel evidence to support the central role of platelets in inflammation.

Original languageEnglish
Pages (from-to)478-483
Number of pages6
JournalThrombosis and Haemostasis
Volume84
Issue number3
Publication statusPublished - 2000

Keywords

  • Apoptosis
  • Human
  • Inflammation
  • Neutrophils
  • Platelets

ASJC Scopus subject areas

  • Hematology

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    Brunetti, M., Martelli, N., Manarini, S., Mascetra, N., Musiani, P., Cerletti, C., Aiello, F. B., & Evangelista, V. (2000). Polymorphonuclear leukocyte apoptosis is inhibited by platelet-released mediators, role of TGFβ-1. Thrombosis and Haemostasis, 84(3), 478-483.