PDF herunterladen
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
› InstitutsangabenThis 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.
Weitere Informationen

Publikationsverlauf

Received 12. Januar 2000

Accepted after revision 03. April 2000

Publikationsdatum:
14. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

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
 

  • References

  • 1 Weksler BB. Roles for human platelets in inflammation. Prog Clin Biol Res 1988; 283: 611-38.
    PubMedGoogle Scholar
  • 2 Del Maschio A, Dejana E, Bazzoni G. Bidirectional modulation of platelet and polymorphonuclear leukocyte activities. Ann Hematol 1993; 67: 23-31.
    CrossrefPubMedGoogle Scholar
  • 3 Evangelista V, Manarini S, Sideri R, Rotondo S, Martelli N, Piccoli A, Totani L, Piccardoni P, Vestweber D, de Gaetano G, Cerletti C. Platelet/ Polymorphonuclear leukocyte interaction: P-selectin triggers protein-tyrosine phosphorylation-dependent CD11b/CD18 adhesion: role of PSGL-1 as a signaling molecule (In Process Citation). Blood 1999; 93: 876-85.
    PubMedGoogle Scholar
  • 4 Piccardoni P, Evangelista V, Piccoli A, de Gaetano G, Walz A, Cerletti C. Thrombin-activated human platelets release two NAP-2 variants that stimulate polymorphonuclear leukocytes. Thromb Haemost 1996; 76: 780-5.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 5 Aziz KA, Cawley JC, Treweeke AT, Zuzel M. Sequential potentiation and inhibition of PMN reactivity by maximally stimulated platelets. J Leukoc Biol 1997; 61: 322-8.
    CrossrefPubMedGoogle Scholar
  • 6 Johnson RJ. Platelets in inflammatory glomerular injury. Semin Nephrol 1991; 11: 276-84.
    PubMedGoogle Scholar
  • 7 Romson JL, Hook BG, Rigot VH, Schork MA, Swanson DP, Lucchesi BR. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction. Circulation 1982; 66: 1002-11.
    CrossrefPubMedGoogle Scholar
  • 8 Bednar M, Smith B, Pinto A, Mullane KM. Neutrophil depletion suppresses 111In-labeled platelet accumulation in infarcted myocardium. J Cardiovasc Pharmacol 1985; 07: 906-12.
    CrossrefPubMedGoogle Scholar
  • 9 Chignard M, Renesto P. Proteinases and cytokines in neutrophil and platelet interactions in vitro. Possible relevance to the adult respiratory distress syndrome. Ann NY Acad Sci 1994; 725: 309-22.
    CrossrefPubMedGoogle Scholar
  • 10 Brus F, van Oeveren W, Okken A, Oetomo SB. Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity. Pediatrics 1997; 99: 672-80.
    CrossrefPubMedGoogle Scholar
  • 11 Gawaz M, Dickfeld T, Bogner C, Fateh-Moghadam S, Neumann FJ. Platelet function in septic multiple organ dysfunction syndrome (see comments). Intensive Care Med 1997; 23: 379-85.
    CrossrefPubMedGoogle Scholar
  • 12 Gawaz M, Fateh-Moghadam S, Pilz G, Gurland HJ, Werdan K. Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure. Eur J Clin Invest 1995; 25: 843-51.
    CrossrefPubMedGoogle Scholar
  • 13 Andonegui G, Trevani AS, Lopez DH, Raiden S, Giordano M, Geffner JR. Inhibition of human neutrophil apoptosis by platelets. J Immunol 1997; 158: 3372-7.
    PubMedGoogle Scholar
  • 14 Homburg CH, Roos D. Apoptosis of neutrophils. Curr Opin Hematol 1996; 03: 94-9.
    CrossrefPubMedGoogle Scholar
  • 15 Savill J. Apoptosis in resolution of inflammation. J Leukoc Biol 1997; 61: 375-80.
    CrossrefPubMedGoogle Scholar
  • 16 Whyte MK, Meagher LC, MacDermot J, Haslett C. Impairment of function in aging neutrophils is associated with apoptosis. J Immunol 1993; 150: 5124-34.
    PubMedGoogle Scholar
  • 17 Vargas JR, Radomski M, Moncada S. The use of prostacyclin in the separation from plasma and washing of human platelets. Prostaglandins 1982; 23: 929-45.
    CrossrefPubMedGoogle Scholar
  • 18 Hawrylowicz CM, Santoro SA, Platt FM, Unanue ER. Activated platelets express IL-1 activity. J Immunol 1989; 143: 4015-8.
    PubMedGoogle Scholar
  • 19 Hawrylowicz CM, Howells GL, Feldmann M. Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production. J Exp Med 1991; 174: 785-90.
    CrossrefPubMedGoogle Scholar
  • 20 Kaplanski G, Porat R, Aiura K, Erban JK, Gelfand JA, Dinarello CA. Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event. Blood 1993; 81: 2492-5.
    PubMedGoogle Scholar
  • 21 Loppnow H, Bil R, Hirt S, Schonbeck U, Herzberg M, Werdan K, Rietschel ET, Brandt E, Flad HD. Platelet-derived interleukin-1 induces cytokine production, but not proliferation of human vascular smooth muscle cells. Blood 1998; 91: 134-41.
    PubMedGoogle Scholar
  • 22 Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 1992; 80: 2012-20.
    PubMedGoogle Scholar
  • 23 Moulding DA, Quayle JA, Hart CA, Edwards SW. Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood 1998; 92: 2495-502.
    PubMedGoogle Scholar
  • 24 Oberhammer FA, Pavelka M, Sharma S, Tiefenbacher R, Purchio AF, Bursch W, Schulte-Hermann R. Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1. Proc Natl Acad Sci USA 1992; 89: 5408-12.
    CrossrefPubMedGoogle Scholar
  • 25 Benassi L, Ottani D, Fantini F, Marconi A, Chiodino C, Giannetti A, Pincelli C. 1,25-dihydroxyvitamin D3, transforming growth factor beta1, calcium, and ultraviolet B radiation induce apoptosis in cultured human keratinocytes. J Invest Dermatol 1997; 109: 276-82.
    CrossrefPubMedGoogle Scholar
  • 26 Yanagisawa K, Osada H, Masuda A, Kondo M, Saito T, Yatabe Y, Takagi K, Takahashi T. Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-beta in human normal lung epithelial cells. Oncogene 1998; 17: 1743-7.
    CrossrefPubMedGoogle Scholar
  • 27 Herbert JM, Carmeliet P. Involvement of u-PA in the anti-apoptotic activity of TGFbeta for vascular smooth muscle cells. FEBS Lett 1997; 413: 401-4.
    CrossrefPubMedGoogle Scholar
  • 28 Flanders KC, Ren RF, Lippa CF. Transforming growth factor-betas in neurodegenerative disease. Prog Neurobiol 1998; 54: 71-85.
    CrossrefPubMedGoogle Scholar
  • 29 Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int 1997; 51: 1376-82.
    CrossrefPubMedGoogle Scholar
  • 30 Hannigan M, Zhan L, Ai Y, Huang CK. The role of p38 MAP kinase in TGF-beta1-induced signal transduction in human neutrophils. Biochem Biophys Res Commun 1998; 246: 55-8.
    CrossrefPubMedGoogle Scholar
  • 31 Frasch SC, Nick JA, Fadok VA, Bratton DL, Worthen GS, Henson PM. p38 mitogen-activated protein kinase-dependent and -independent intracellular signal transduction pathways leading to apoptosis in human neutrophils. J Biol Chem 1998; 273: 8389-97.
    CrossrefPubMedGoogle Scholar
  • 32 Cohen P. The search for physiological substrates of MAP and SAP kinases in mammalian cells. Trends Cell Biol 1997; 07: 353-61.
    CrossrefPubMedGoogle Scholar
  • 33 Yan Z, Zhang J, Holt JC, Stewart GJ, Niewiarowski S, Poncz M. Structural requirements of platelet chemokines for neutrophil activation. Blood 1994; 84: 2329-39.
    PubMedGoogle Scholar
  • 34 Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem 1983; 258: 7155-60.
    PubMedGoogle Scholar
  • 35 Assoian RK, Sporn MB. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol 1986; 102: 1217-23.
    CrossrefPubMedGoogle Scholar
  • 36 Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem 1988; 263: 7646-54.
    PubMedGoogle Scholar
  • 37 Miyazono K, Hellman U, Wernstedt C, Heldin CH. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem 1988; 263: 6407-15.
    PubMedGoogle Scholar
  • 38 Grainger DJ, Wakefield L, Bethell HW, Farndale RW, Metcalfe JC. Release and activation of platelet latent TGF-beta in blood clots during dissolution with plasmin. Nat Med 1995; 01: 932-7.
    CrossrefPubMedGoogle Scholar
  • 39 Muzio M, Sironi M, Polentarutti N, Mantovani A, Colotta F. Induction by transforming growth factor-beta 1 of the interleukin-1 receptor antagonist and of its intracellular form in human polymorphonuclear cells. Eur J Immunol 1994; 24: 3194-8.
    CrossrefPubMedGoogle Scholar
  • 40 Dubois CM, Ruscetti FW, Palaszynski EW, Falk LA, Oppenheim JJ, Keller JR. Transforming growth factor beta is a potent inhibitor of interleukin 1 (IL-1) receptor expression: proposed mechanism of inhibition of IL-1 action. J Exp Med 1990; 172: 737-44.
    CrossrefPubMedGoogle Scholar
  • 41 Harvey AK, Hrubey PS, Chandrasekhar S. Transforming growth factorbeta inhibition of interleukin-1 activity involves down-regulation of interleukin-1 receptors on chondrocytes. Exp Cell Res 1991; 195: 376-85.
    CrossrefPubMedGoogle Scholar
  • 42 Brach MA, deVos S, Gruss HJ, Herrmann F. Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colonystimulating factor is caused by inhibition of programmed cell death. Blood 1992; 80: 2920-4.
    PubMedGoogle Scholar
  • 43 Lagraoui M, Gagnon L. Enhancement of human neutrophil survival and activation by TGF-beta 1. Cell Mol Biol (Noisy-le-grand) 1997; 43: 313-8.
    PubMedGoogle Scholar
  • 44 Ward C, Hannah S, Chilvers ER, Farrow S, Haslett C, Rossi AG. Transforming growth factor-beta increases the inhibitory effects of GM-CSF and dexamethasone on neutrophil apoptosis. Biochem Soc Trans 1997; 25: 244S.
    CrossrefPubMedGoogle Scholar
  • 45 Vassallo Jr RR, Kieber-Emmons T, Cichowski K, Brass LF. Structurefunction relationships in the activation of platelet thrombin receptors by receptor-derived peptides. J Biol Chem 1992; 267: 6081-5.
    PubMedGoogle Scholar
  • 46 Schultz-Cherry S, Ribeiro S, Gentry L, Murphy-Ullrich JE. Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a chemically defined system. J Biol Chem 1994; 269: 26775-82.
    PubMedGoogle Scholar
  • 47 Schultz-Cherry S, Chen H, Mosher DF, Misenheimer TM, Krutzsch HC, Roberts DD, Murphy-Ullrich JE. Regulation of transforming growth factorbeta activation by discrete sequences of thrombospondin 1. J Biol Chem 1995; 270: 7304-10.
    CrossrefPubMedGoogle Scholar
  • 48 Schultz-Cherry S, Murphy-Ullrich JE. Thrombospondin causes activation of latent transforming growth factor- beta secreted by endothelial cells by a novel mechanism [published erratum appears in J Cell Biol 1993 Sep; 122 (5):following 1143]. J Cell Biol 1993; 122: 923-32.
    CrossrefPubMedGoogle Scholar
  • 49 Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP, Bouck N. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell 1998; 93: 1159-70.
    CrossrefPubMedGoogle Scholar
  • 50 Moriguchi T, Kuroyanagi N, Yamaguchi K, Gotoh Y, Irie K, Kano T, Shirakabe K, Muro Y, Shibuya H, Matsumoto K, Nishida E, Hagiwara M. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem 1996; 271: 13675-9.
    CrossrefPubMedGoogle Scholar
  • 51 Schnyder B, Meunier PC, Car BD. Inhibition of kinases impairs neutrophil activation and killing of Staphylococcus aureus. Biochem J 1998; 331: 489-95.
    CrossrefPubMedGoogle Scholar
  • 52 Detmers PA, Zhou D, Polizzi E, Thieringer R, Hanlon WA, Vaidya S, Bansal V. Role of stress-activated mitogen-activated protein kinase (p38) in beta 2-integrin-dependent neutrophil adhesion and the adhesion-dependent oxidative burst. J Immunol 1998; 161: 1921-9.
    PubMedGoogle Scholar
  • 53 Stylianou E, Saklatvala J. Interleukin-1. Int J Biochem Cell Biol 1998; 30: 1075-9.
    CrossrefPubMedGoogle Scholar
  • 54 McLeish KR, Knall C, Ward RA, Gerwins P, Coxon PY, Klein JB, Johnson GL. Activation of mitogen-activated protein kinase cascades during priming of human neutrophils by TNF-alpha and GM-CSF. J Leukoc Biol 1998; 64: 537-45.
    CrossrefPubMedGoogle Scholar
  • 55 Zu YL, Qi J, Gilchrist A, Fernandez GA, Vazquez-Abad D, Kreutzer DL, Huang CK, Sha’afi RI. p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-alpha or FMLP stimulation. J Immunol 1998; 160: 1982-9.
    PubMedGoogle Scholar
  • 56 Nahas N, Molski TF, Fernandez GA, Sha’afi RI. Tyrosine phosphorylation and activation of a new mitogen-activated protein (MAP)-kinase cascade in human neutrophils stimulated with various agonists. Biochem J 1996; 318: 247-53.
    CrossrefPubMedGoogle Scholar
  • 57 Nick JA, Avdi NJ, Gerwins P, Johnson GL, Worthen GS. Activation of a p38 mitogen-activated protein kinase in human neutrophils by lipopolysaccharide. J Immunol 1996; 156: 4867-75.
    PubMedGoogle Scholar