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Inflammation Research
Published in: Inflammation Research 3-4/2015

01-04-2015 | Original Research Paper

Circulating levels of platelet α-granule cytokines in trauma patients

Authors: N. A. Windeløv, S. R. Ostrowski, P. I. Johansson, M. Wanscher, C. F. Larsen, A. M. Sørensen, L. S. Rasmussen

Published in: Inflammation Research | Issue 3-4/2015

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Abstract

Objective and design

To elucidate whether platelets differentiate cytokine release following trauma, we prospectively measured three major platelet-derived cytokines in 213 trauma patients on hospital arrival.

Methods

We measured plasma levels of the anti-inflammatory β-thromboglobulins (βTGs), transforming growth factor-β1 (TGFβ1) and the pro-inflammatory platelet factor 4 (PF4) cytokines. We also measured soluble glycoprotein VI (sGPVI), procoagulant platelet microparticles (PMPs) and white blood cell (WBC) counts, and evaluated in vitro platelet function in primary and secondary haemostasis by aggregometry and thromboelastometry, respectively. We evaluated associations of each cytokine by multivariate regression including injury severity score (ISS), WBC counts, sGPVI and platelet counts as explanatory variables.

Results

Severely injured patients (ISS > 15) had higher levels of βTGs and TGFβ1 (both p < 0.01) but lower levels of PF4 (p = 0.02). GPVI and PMPs levels correlated with TGFβ1 and PF4 whereas we found no significant association between cytokine levels and measures of haemostasis. By multivariate regression, a high WBC count was associated with high levels of TGFβ1 (p = 0.01) and βTGs (p < 0.01) but with low levels of PF4 (p = 0.03).

Conclusion

Severely injured patients had higher levels of βTGs and TGFβ1 but lower levels of the PF4; a high WBC count predicted this anti-inflammatory profile of platelet cytokines.
Literature
1.
2.
McGhan LJ, Jaroszewski DE. The role of toll-like receptor-4 in the development of multi-organ failure following traumatic haemorrhagic shock and resuscitation. Injury. 2012;43(2):129–36.CrossRefPubMed
3.
Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104–7.CrossRefPubMedCentralPubMed
4.
5.
Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 2011;118(7):1952–61.CrossRefPubMedCentralPubMed
6.
Panigrahi S, Ma Y, Hong L, Gao D, West XZ, Salomon RG, et al. Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis. Circ Res. 2013;112(1):103–12.CrossRefPubMedCentralPubMed
7.
Cox D, Kerrigan SW, Watson SP. Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation. J Thromb Haemost. 2011;9(6):1097–107.CrossRefPubMed
8.
Projahn D, Koenen RR. Platelets: key players in vascular inflammation. J Leukoc Biol. 2012;92(6):1167–75.CrossRefPubMed
9.
Fujimi S, MacConmara MP, Maung AA, Zang Y, Mannick JA, Lederer JA, et al. Platelet depletion in mice increases mortality after thermal injury. Blood. 2006;107(11):4399–406.CrossRefPubMedCentralPubMed
10.
Ostrowski SR, Johansson PI. Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness. Med Hypotheses. 2011;77(5):798–802.CrossRefPubMed
11.
Golebiewska EM, Poole AW. Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev. 2014 (in press).
12.
Woronowicz K, Dilks JR, Rozenvayn N, Dowal L, Blair PS, Peters CG, et al. The platelet actin cytoskeleton associates with SNAREs and participates in alpha-granule secretion. Biochemistry. 2010;49(21):4533–42.CrossRefPubMedCentralPubMed
13.
El Golli N, Issertial O, Rosa J-P, Briquet-Laugier V. Evidence for a granule targeting sequence within platelet factor 4. J Biol Chem. 2005;280(34):30329–35.CrossRefPubMed
14.
Rönnlund D, Yang Y, Blom H, Auer G, Widengren J. Fluorescence nanoscopy of platelets resolves platelet-state specific storage, release and uptake of proteins, opening up future diagnostic applications. Adv Healthc Mater. 2012;1(6):707–13.CrossRefPubMed
15.
Rex S, Beaulieu LM, Perlman DH, Vitseva O, Blair PS, McComb ME, et al. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions, and alpha-granule release. Thromb Haemost. 2009;102(1):97–110.PubMedCentralPubMed
16.
Vandercappellen J, Van Damme J, Struyf S. The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer. Cytokine Growth Factor Rev. 2011;22(1):1–18.CrossRefPubMed
17.
Windeløv NA, Sørensen AM, Perner A, Wanscher M, Larsen CF, Ostrowski SR, et al. Platelet aggregation following trauma: a prospective study. Blood Coagul Fibrinolysis. 2014;25(1):67–73.CrossRefPubMed
18.
Windeløv NA, Johansson PI, Sørensen AM, Perner A, Wanscher M, Larsen CF, et al. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients. J Trauma Acute Care Surg. 2014;77(5):692–700.CrossRefPubMed
19.
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1481–3.CrossRefPubMed
20.
Tohira H, Jacobs I, Mountain D, Gibson N, Yeo A. Comparisons of the Outcome Prediction Performance of Injury Severity Scoring Tools Using the Abbreviated Injury Scale 90 Update 98 (AIS 98) and 2005 Update 2008 (AIS 2008). Ann Adv Automot Med. 2011;55:255–65.PubMedCentralPubMed
21.
Gentile LF, Cuenca AG, Vanzant EL, Efron PA, McKinley B, Moore F, Moore F, et al. Is there value in plasma cytokine measurements in patients with severe trauma and sepsis? Methods. 2013;61(1):3–9.CrossRefPubMedCentralPubMed
22.
Heizmann O, Koeller M, Muhr G, Oertli D, Schinkel C. Th1- and Th2-type cytokines in plasma after major trauma. J Trauma. 2008;65(6):1374–8.CrossRefPubMed
23.
Botha AJ, Moore FA, Moore EE, Sauaia A, Banerjee A, Peterson VM. Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. J Trauma. 1995;39(3):411–7.CrossRefPubMed
24.
Stephens G, Yan Y, Jandrot-Perrus M, Villeval J-L, Clemetson KJ, Phillips DR. Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen. Blood. 2005;105(1):186–91.CrossRefPubMed
25.
Al-Tamimi M, Grigoriadis G, Tran H, Paul E, Servadei P, Berndt MC, et al. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa. Blood. 2011;117(14):3912–20.CrossRefPubMed
26.
Al-Tamimi M, Arthur JF, Gardiner E, Andrews RK. Focusing on plasma glycoprotein VI. Thromb Haemost. 2012;107(4):648–55.CrossRefPubMed
27.
Ivandic BT, Spanuth E, Haase D, Lestin H-G, Katus HA. Increased plasma concentrations of soluble CD40 ligand in acute coronary syndrome depend on in vitro platelet activation. Clin Chem. 2007;53(7):1231–4.CrossRefPubMed
28.
Kaplan KL, Owen J. Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood. 1981;57(2):199–202.PubMed
29.
30.
Poon TCW, Pang RTK, Chan KCA, Lee NLS, Chiu RWK, Tong Y-K, et al. Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome. Electrophoresis. 2012;33(12):1894–900.CrossRefPubMed
31.
Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med. 2000;28(2):451–7.CrossRefPubMed
32.
Idell S, Maunder R. Platelet-specific alpha-granule proteins and thrombospondin in bronchoalveolar lavage in the adult respiratory distress syndrome. Chest. 1989;96:1125–32.CrossRefPubMed
33.
Kurabayashi H, Tamura J, Naruse T, Kubota K. Possible existence of platelet activation before the onset of cerebral infarction. Atherosclerosis. 2000;153(1):203–7.CrossRefPubMed
34.
Riza Erbay A, Turhan H, Aksoy Y, Senen K, Yetkin E. Activation of coagulation system in dilated cardiomyopathy: comparison of patients with and without left ventricular thrombus. Coron Artery Dis. 2004;15(5):265–8.CrossRefPubMed
35.
Nichols a B, Owen J, Kaplan KL, Sciacca RR, Cannon PJ, Nossel HL. Fibrinopeptide A, platelet factor 4, and beta-thromboglobulin levels in coronary heart disease. Blood. 1982;60(3):650–4.PubMed
36.
Bellon JL, Castellanos C, Acevedo L, Amiral J. Measurement of beta-thromboglobulin and platelet factor 4 to follow up patients with artificial heart valves. Semin Thromb Hemost. 1993;19(Suppl 1):178–82.PubMed
37.
Lapchak PH, Ioannou A, Rani P, Lieberman LA, Yoshiya K, Kannan L, et al. The role of platelet factor 4 in local and remote tissue damage in a mouse model of mesenteric ischemia/reperfusion injury. PLoS ONE. 2012;7(7):e39934.CrossRefPubMedCentralPubMed
38.
Kowalska MA, Mahmud SA, Lambert MP, Poncz M, Slungaard A. Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge. Blood. 2013;110:1903–5.CrossRef
39.
Stringer SE, Gallagher JT. Specific binding of the chemokine platelet factor 4 to heparan sulfate. J Biol Chem. 1997;272(33):20508–14.CrossRefPubMed
40.
Slungaard A. Platelet factor 4 modulation of the thrombomodulin–protein C system. Crit Care Med. 2004;32(Suppl):S331–5.CrossRefPubMed
41.
Grainger DJ, Mosedale DE, Metcalfe JC. TGF-beta in blood: a complex problem. Cytokine Growth Factor Rev. 2000;11(1–2):133–45.CrossRefPubMed
42.
Miyoshi H, Ajima R, Luo CT, Yamaguchi TP, Stappenbeck TS. Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury. Science. 2012;338(6103):108–13.CrossRefPubMedCentralPubMed
43.
Kim M, Park SW, Kim M, D’Agati VD, Lee HT. Isoflurane post-conditioning protects against intestinal ischemia-reperfusion injury and multiorgan dysfunction via transforming growth factor-β1 generation. Ann Surg. 2012;255(3):492–503.CrossRefPubMedCentralPubMed
44.
West SD, Goldberg D, Ziegler A, Krencicki M, Du Clos TW, Mold C. Transforming growth factor-β, macrophage colony-stimulating factor and C-reactive protein levels correlate with CD14(high)CD16+ monocyte induction and activation in trauma patients. PLoS ONE. 2012;7(12):e52406.CrossRefPubMedCentralPubMed
45.
Laun RA, Schröder O, Schoppnies M, Röher H-D, Ekkernkamp A, Schulte K-M. Transforming growth factor-beta1 and major trauma: time-dependent association with hepatic and renal insufficiency. Shock. 2003;19(1):16–23.CrossRefPubMed
46.
Davenport RA, Brohi K. Coagulopathy in trauma patients: importance of thrombocyte function? Curr Opin Anaesthesiol. 2009;22(2):261–6.CrossRefPubMed
47.
Michelson AD, Barnard MR, Hechtman HB, MacGregor H, Connolly RJ, Loscalzo J, et al. In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci USA. 1996;93(21):11877–82.CrossRefPubMedCentralPubMed
Metadata
Title
Circulating levels of platelet α-granule cytokines in trauma patients
Authors
N. A. Windeløv
S. R. Ostrowski
P. I. Johansson
M. Wanscher
C. F. Larsen
A. M. Sørensen
L. S. Rasmussen
Publication date
01-04-2015
Publisher
Springer Basel
Published in
Inflammation Research / Issue 3-4/2015
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-015-0802-4

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